Arthritis

Breakthrough Offers Potential Treatment For Rheumatoid Arthritis

2011-07-03T00:00:00.000-07:00

A breakthrough in understanding the way atoms move across cell membranes in the human body could pave the way for the development of new treatments for inflammatory diseases such as rheumatoid arthritis.

Scientists at the University of Leeds have identified a previously unknown natural mechanism that opens ion channels - proteins at the cell surface that act as doorways into and out of cells - through the naturally occurring protein thioredoxin.

Ion channels allow movement of ions - electrically charged atoms - across the cell membrane to carry out various functions such as pain transmission, timing of the heart beat, and regulation of blood glucose. Often, they need to be stimulated to open and, until now, two main groups of activating mechanisms have been acknowledged: changes in cell voltage and binding of chemical factors.

In a paper published today (03 January) in Nature, Professor Beech and colleagues from the University's Faculty of Biological Sciences reveal that thioredoxin works in a different manner: it activates an ion channel by donating electrons to it, in a process Professor Beech likens to "an electronic on-switch".

"Thioredoxin is naturally present in cells and is secreted to help the body counter stressful chemical reactions that occur in inflammation, which can damage cells," he explains. "We already knew that inflammatory diseases cause the production of high levels of thioredoxin - in fact with rheumatoid arthritis, it's striking how much is present in affected joints. But we didn't know until now that thioredoxin can also activate ion channels, conferring additional protective potential and offering opportunities for mimicking the effect with drugs."

"It would seem that the body's own natural defences have provided us with new understanding that could be significant in the development of future treatments for arthritis and related diseases," he says.

The research has been funded by the Wellcome Trust, which has recently provided the group with further funding to expand its research into ion channels.

Source: Jo Kelly

University of Leeds

Rheumatoid Arthritis Patients Taking Enbrel® Keep Working For Longer

2011-07-01T23:45:00.000-07:00

Patients receiving Enbrel® (etanercept) in combination with methotrexate for early Rheumatoid Arthritis (RA) are more likely to continue working, according to the COMET study published recently in Rheumatology.

One year results from the COMET study - which compared the impact of methotrexate alone with methotrexate in combination with Enbrel on work productivity - showed that active early RA patients receiving the Enbrel-methotrexate combination were nearly three times less likely to stop working compared to patients receiving methotrexate alone. Furthermore, work absenteeism was reduced by almost 50 per cent in the combination group.1

RA is a chronic and progressive disease that affects 2.9 million people across Europe.2 As the disease progresses, RA can cause permanent damage to the joints, resulting in deformity and loss of independence.

The prevention of work productivity loss represents benefit beyond the traditional measures of disease improvement. The economic impact of RA is significant, with an estimated €45 billion spent on the disease in Europe each year. Of this, 32 per cent of the total cost is likely due to work disability and decrease in work productivity.2 Results from previous studies suggest that even in the early stages of disease, RA can impact a person's ability to work.1 In the COMET study, half of the work stoppages observed occurred in the first three months of the trial.1

"Keeping a person gainfully employed represents a benefit to society, above and beyond, the clinical benefits of treatment" said Professor Aslam Anis, School of Population and Public Health, University of British Columbia and lead author of the paper. "The fact that half of the work stoppages occurred in the first three months of this trial, together with the fact that there were significantly fewer work stoppages in the Enbrel-methotrexate combination group, underscore the importance of early and aggressive treatment of RA."

During the COMET (COmbination of Methotrexate and ETanercept) study, work absenteeism was recorded over 12 months amongst 205 patients with early active RA. Total absenteeism was defined as a composite of number of missed workdays, reduced working time and number of days patients were unemployed as a result of their RA.

At the end of one year:1
The number of missed workdays in the group receiving combination treatment of Enbrel and methotrexate (14.2 days) was approximately half that of patients receiving methotrexate monotherapy (31.9 days)

In total, the Enbrel combination group missed up to 37 fewer total days due to absenteeism than the methotrexate monotherapy group

24 per cent of patients in the monotherapy group had to stop work at least once during the year, compared to 8.6 per cent of patients in the combination therapy group

Previously published data from the COMET trial showed that early treatment of RA can halt the joint damage seen as the disease progresses - 80 per cent of patients in the combination group experienced no further joint damage as measured by x-rays. Furthermore, 50 per cent of patients experienced a sustained reduction in disease activity as measured by the number of swollen joints (i.e. clinical remission) and 55 per cent achieved normal physical functioning, as measured by the Health Assessment Questionnaire.3

About COMET

The COMET (COmbination of Methotrexate and ETanercept in early rheumatoid arthritis) study was designed to compare the clinical efficacy and safety of Enbrel (ETN) and methotrexate (MTX) combination therapy with MTX alone on clinical disease activity and progressive joint damage in patients with active early rheumatoid arthritis. The work analysis was designed to compare the impact of ETN+MTX to MTX alone on work productivity among MTX-na??ve patients with active early RA over 12 months.

Two hundred and five patients [MTX (n=100) VS ETN+MTX (n=1050], who were working full time or part time at the start of the trial and had at least one follow-up observation, were included in the analysis. Compared with the MTX group, the ETN+MTX group had a maximum of 37 fewer missed workdays or at minimum 22 fewer missed workdays.

About ENBREL

ENBREL is a fully human soluble tumour necrosis factor (TNF) receptor antagonist. ENBREL was first approved in 1998 for moderate to rheumatoid arthritis and has since been used in 505,000 patients worldwide across indications.

ENBREL is approved for the following indications:

Rheumatoid arthritis
ENBREL in combination with methotrexate is indicated for the treatment of moderate to severe active rheumatoid arthritis in adults when the response to disease-modifying antirheumatic drugs, including methotrexate (unless contraindicated), has been inadequate. ENBREL can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate. ENBREL is also indicated in the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate. ENBREL, alone or in combination with methotrexate, has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function.

Polyarticular juvenile idiopathic arthritis
Treatment of active polyarticular juvenile idiopathic arthritis in children and adolescents aged 4 to 17 years who have had an inadequate response to, or who have proved intolerant of, methotrexate. ENBREL has not been studied in children aged less than 4 years.

Psoriatic arthritis
Treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying antirheumatic drug therapy has been inadequate. ENBREL has been shown to improve physical function in patients with psoriatic arthritis, and to reduce the rate of progression of peripheral joint damage as measured by X-ray in patients with polyarticular symmetrical subtypes of the disease.

Ankylosing spondylitis
Treatment of adults with severe active ankylosing spondylitis who have had an inadequate response to conventional therapy.

Plaque psoriasis
Treatment of adults with moderate to severe plaque psoriasis who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or PUVA. ENBREL is also licensed in the European Union for treatment of chronic severe plaque psoriasis in children and adolescents from the age of 8 years who are inadequately controlled by, or are intolerant to, other systemic therapies or phototherapies.

About Wyeth

Wyeth Pharmaceuticals, a division of Wyeth, has leading products in the areas of women's health care, infectious disease, gastrointestinal health, central nervous system, inflammation, transplantation, haemophilia, oncology, vaccines and nutritional products.

Wyeth is one of the world's largest research-driven pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing and marketing of pharmaceuticals, vaccines, biotechnology products, nutritionals and non-prescription medicines that improve the quality of life for people worldwide. The Company's major divisions include Wyeth Pharmaceuticals, Wyeth Consumer Healthcare and Fort Dodge Animal Health.

References

1. Anis A et al. The effect of etanercept on work productivity in patients with early active rheumatoid arthritis: results from the COMET study. Rheumatology doi:10.1093/rheumatology/kep239. E-Pub, 18 August 2009

2. Lundkvistet al. The burden of rheumatoid arthritis and access to treatment: health burden and costs. Eur J Health Econ 2008;8 (Suppl.2):S49-60

3. Emery P et al. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet. 2008;372:375-382

Source:

Wyeth

View drug information on Enbrel.

New Biologic Drug Is Effective Against Rheumatoid Arthritis

2011-06-30T23:30:00.000-07:00

Abatacept, a member of a new class of drug that targets immune cells to treat rheumatoid arthritis (RA), is effective against RA, according to a new Cochrane Systematic Review. The review examines recent trials to assess safety and efficacy of the drug.

RA is an autoimmune disease affecting up to 1 in 100 people in Western countries. RA patients experience chronic pain and inflammation as a result of the body's own immune system attacking the lining of the joints. Abatacept is a new "biologic" drug that works by blocking the actions of the immune cells, called T cells, which cause joint inflammation.

The review combined data from seven trials including 2,908 patients, whose symptoms were assessed after one year of taking the drug or a placebo. Compared to placebo, patients given abatacept were twice as likely to achieve a 50% improvement in symptoms, including pain and the number of tender and swollen joints. Patients who took the drug also experienced improvements in physical ability. There was no progression in damage to joints of people who took abatacept at 12 months follow up. However, serious adverse effects increased if the drug was given in combination with other biologics.

"Like other biologics, abatacept is an expensive drug, but if the benefits are evident, it may be of great interest to patients with rheumatoid arthritis who fail standard therapy or other biologic treatment. Our review shows that it is indeed effective, and generally well-tolerated, but we would strongly recommend that it is not used with other biologics," says lead researcher, Lara Maxwell, of the Institute of Population Health at the University of Ottawa in Ontario, Canada.

"There is a need for more long term studies to determine whether the drug is safe and the effect sustained over longer periods. Better designed studies in the future are likely to have a longer follow-up and high retention rates, and it would be useful to conduct trials of one biologic versus another."

Source:
Jennifer Beal

Wiley-Blackwell

Adalimumab Proves Effective For Children With Juvenile Rheumatoid Arthritis

2011-06-29T23:15:00.000-07:00

Adalimumab, an injectable anti-TNF therapy that has FDA approval for treating rheumatoid arthritis in adults, has proven effective in children with juvenile rheumatoid arthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Washington, DC.

The immunosuppressant adalimumab, currently used to treat adults with moderate to severe rheumatoid arthritis, targets inflammation by blocking TNF (tumor necrosis factor) proteins in the body. Following studies that demonstrated safety and effectiveness in adults with rheumatoid arthritis, this study in children with juvenile rheumatoid arthritis was performed. Juvenile rheumatoid arthritis affects an estimated 285,000 children in the U.S. The disease, which starts before they reach age 16, can cause joint stiffness, reluctance or refusal to use arms or legs, reduced activity levels, persistent pain and joint swelling. If not effectively treated, it can result in joint damage, growth delay and decreased bone mineralization.

To assess the long-term effectiveness and safety of adalimumab in a younger population, researchers conducted a 48-week randomized study on 171 children, ages 4 to 17, with five or more swollen joints and three or more joints with limited range of motion at the outset of the study. The subjects were categorized as those taking and not taking methotrexate at the beginning of the study. The dose of methotrexate and all other arthritis medications remained stable throughout the trial. Adalimumab doses were based on the child's size, with participants receiving 24 mg/M2 BSA, maximum of 40 mg, given as a subcutaneous injection every 2 weeks over a 16-week period. At the end of the 16 weeks, the 83% (142) of the subjects who met the definition of "responder" for this study were randomized into a double-blind study and assigned to either continue adalimumab or switch to a placebo for the next 32 weeks or until disease flare-up.

Results demonstrated that participants receiving adalimumab had significantly fewer disease flares than those on placebo. Of those not already taking methotrexate, 43% randomized to adalimumab and 71% to placebo flared; of those already on methotrexate, 37% and 65%, respectively flared. The most common problems were mild upper respiratory infections. No tuberculosis or opportunistic infections were reported.

"Based on this data, adalimumab taken with or without methotrexate provided rapid, substantial and sustainable improvement for children with very active juvenile rheumatoid arthritis," explains Daniel J. Lovell, MD, MPH, Chairman, Pediatric Rheumatology Collaborative Study Group, Cincinnati, Ohio and an investigator in the study. "Given that the medication was generally well tolerated, adalimumab has emerged as an excellent treatment option for children with juvenile rheumatoid arthritis."

The American College of Rheumatology is the professional organization for rheumatologists and health professionals who share a dedication to healing, preventing disability and curing arthritis and related rheumatic and musculoskeletal diseases. For more information on the ACR's annual meeting, see rheumatology/annual.

Presentation Number: 659

Long-Term Efficacy and Safety of Adalimumab in Children with Juvenile Rheumatoid Arthritis (JRA): 48-Week Results

D. J. Lovell1, N. Ruperto2, L. Jung1, A. Reiff3, D. Nemcova2, K. Jarosova2, A. Prieur2, C. Sandborg1, J. Rovensky2, J. Bohnsack1, K. Minden2, L. Wagner Weiner1, R. Vehe1, G. Horneff2, J. Medich4, E. H. Giannini1, A. Martini2. 1PRCSG, Cincinnati, OH; 2PRINTO-IRCCS G Gaslini, Genova, Italy; 3Children's Hospital of Los Angeles, Los Angeles, CA; 4Abbott, Parsipanny, NJ

PURPOSE: This analysis evaluated long-term efficacy and safety of adalimumab (ADA) in pts with JRA.

METHODS: A multi-center, Phase III, randomized, double-blind (DB), placebo (PBO)-controlled withdrawal study was conducted in 171 polyarticular-course JRA pts 4-17 years old with >5 swollen joints and >3 joints with limitation of motion at baseline. At the end of a 16-wk OL phase, pts demonstrating an ACR Ped 30 response were randomized (DB) to either ADA 24 mg /m2 BSA (max 40 mg/dose) or PBO sc eow for an additional 32 wks or until disease flare (primary endpoint). Disease flare criteria were 1) worsening of >30% from baseline in >3 of 6 ACR Ped core criteria, 2) >2 active joints, and 3) improvement of >30% in no more than 1 of the 6 criteria. After 32 wks or at time of flare in DB, pts were allowed to receive OL ADA. Randomization was stratified by use of concomitant MTX. Efficacy and safety assessments were collected at regular intervals.

RESULTS: At the end of the 16-wk OL phase, the % of pts showing ACR Ped 30/50/70 response were 83/74/52. A total of 133 pts entered the DB phase (female, 77%, mean age, 11.2 years, and 65% taking MTX). Only 4% of those entering the DB dropped out (1 protocol violation, 1 withdrew consent, 3 other). In the DB, pts receiving ADA had significantly fewer disease flares than PBO, both without MTX (43.3% vs. 71.4%, p=0.031, primary endpoint) and with MTX (36.8% vs. 64.9%, p=0.015). In ADA pts, ACR30/50/70 responses at Wk 48 (end of DB period) were significantly greater than those in PBO pts (table). Pts who flared in the DB still had good ACR response rates (ACR30/50/70 of 73/61/24) at the time of flare because of stringent flare criteria. Most common AEs were infections (mostly mild upper respiratory). Four ADA and two PBO pts experienced SAEs during the DB phase. No TB or opportunistic infections were reported.

Pediatric ACR Responders at Week 48

ADA PBO

(n=68) (n=65)

ACR30 60%* 35%

ACR50 59%* 35%

ACR70 56%* 28%

p

Celecoxib Increases Risk Of Heart Attack, New Study Finds

2011-06-28T23:00:00.000-07:00

A study published in the March issue of the Journal of the Royal Society of Medicine, has found celecoxib increases the risk of a heart attack by over two-fold.

Celecoxib is the most commonly used COX-2 inhibitor drug in the treatment of arthritis and acute pain. It is manufactured by Pfizer and marketed under the brand name Celebrex.

"Our evidence shows an increased risk of heart attack in patients taking celecoxib," said Professor Richard Beasley of New Zealand's Medical Research Institute.

"Drug regulatory authorities need to urgently re-examine the assessment of the drug in light of these findings."

Cyclooxygenase-2 (COX-2) inhibitor drugs are popular analgesics as they have fewer gastrointestinal side effects than traditional NSAIDs like ibuprofen and diclofenac. However, the extent to which use of COX-2 inhibitors increase the risk of cardiovascular events has been the subject of considerable debate in the last two years.

Rofecoxib, also a COX-2 inhibitor drug, was manufactured by drug company Merck under the name Vioxx but voluntarily withdrawn worldwide following evidence linking it to an increase in the risk of heart attacks and stroke.

Professor Beasley undertook a systematic review and meta-analysis of randomized double-blind clinical trials of celecoxib of at least six weeks' duration and which presented data on serious cardiovascular events.

Specifically, the researchers examined whether the increased risk of cardiovascular events with rofecoxib was also present with celecoxib and thus represented a class effect of COX-2 inhibitors.

Four placebo-controlled trials with 4422 patients were included in the primary meta-analysis comparing celecoxib with placebo. The findings show the use of celecoxib was associated with a 2.26-fold increased risk of myocardial infarction when compared to a placebo.

The second meta-analysis included a total of six studies of 12,780 patients and demonstrated a 1.88-fold increased risk of myocardial infarction when celecoxib was compared with all comparator treatment groups including ibuprofen, paracetomol and diclofenac.

"These findings are critical as the risk is similar in magnitude to the 2.24-fold increased risk of heart attack with Vioxx as reported in a comparable meta-analysis," said Professor Beasley.

"Given the popularity of celecoxib in the treatment of arthritis, drug regulators must undertake an up-to-date risk assessment based on the findings presented here."

Currently, the European Medicines Agency's advice is COX-2 inhibitors should not be used in patients with heart disease or stroke and doctors should use the lowest effective dose of the COX-2 medicine for the shortest possible duration of treatment.

"It will be interesting to see if the drug regulators tighten restrictions and whether celecoxib is now withdrawn as occurred with Vioxx," Professor Beasley said.

JRSM Editor, Kamran Abbasi, said controversy had raged for almost two years about the safety of this class of drug.

"The early warnings on Vioxx went unheeded. We can only hope that clinicians and regulatory authorities around the world will not make the same mistake twice. This is another lesson that wonder drugs often come with a sting in the tail," Dr Abbasi said.

In contrast to the increased risk of myocardial infarction, this study did not identify a corresponding increased risk of cerebrovascular events.

'Risk of cardiovascular events and celecoxib: a systematic review and meta-analysis' by B Caldwell, S Aldington, M Weatherall, P Shirtcliffe and R Beasley is published in the March issue (Vol. 99) of the Journal of the Royal Society of Medicine.

JRSM is the flagship journal of the Royal Society of Medicine. It has been published continuously since 1809. Its Editor is Dr Kamran Abbasi.

Founded in 1805, the Royal Society of Medicine is an independent organisation that promotes the exchange of knowledge, information and ideas in medical science and continued improvement in human health. rsm.ac.uk

View drug information on Vioxx.

Cartilage Repair Hope Offered By Stem Cells Tor Arthritis Sufferers

2011-06-27T22:45:00.000-07:00

Research presented at the UK National Stem Cell Network Annual Science Meeting in Edinburgh could offer hope that bone stem cells may be harnessed to repair the damaged cartilage that is one of the main symptoms of osteoarthritis.

Scientists at Cardiff University have successfully identified stem cells within articular cartilage of adults, which although it cannot become any cell in the body like full stem cells, has the ability to derive into chondrocytes - the cells that make up the body's cartilage - in high enough numbers to make treatment a realistic possibility. The team have even been able to identify the cells in people over 75 years of age.

Osteoarthritis affects over 2M people in the UK and occurs when changes in the make up of the body's cartilage causes joints to fail to work properly. At its worse it can cause the break up of cartilage, causing the ends of the bones in the joint to rub against each other. This results in severe pain and deformation of the joint. One current treatment to treat damaged cartilage due to trauma in younger patients is to harvest cartilage cells from neighbouring healthy cartilage and transplant them into the damaged area. Unfortunately, only a limited number of cells can be generated.

The research team, funded by the Arthritis Research Campaign and the Swiss AO Foundation, have identified a progenitor, or a partially derived stem cell in bovine cartilage that can be turned into can be turned into a chondrocyte in culture. Their breakthrough came in identifying a similar cell in human cartilage that was more like a stem cell with characteristics that they could be used to treat cartilage lesions due to trauma but also mark the onset of osteoarthritis

Lead researcher Professor Charlie Archer from the Cardiff School of Biosciences said: "We have identified a cell which when grown in the lab can produce enough of a person's own cartilage that it could be effectively transplanted. There are limitations in trying to transplant a patient's existing cartilage cells but by culturing it from a resident stem cell we believe we can overcome this limitation.

"This research could have real benefits for arthritis sufferers and especially younger active patients with cartilage lesions that can progress to whole scale osteoarthritis."

Prof Archer commented: "We have embarked on the next stage which is to conduct and animal trial which is a necessary pre-requisite to a clinical trial which we hope to start next year if the results are positive"

This research was presented at the UK National Stem Cell Network Inaugural Science Meeting at the Edinburgh Conference Centre on 11 April 2008.

The conference is a showcase of the best and latest UK stem cell science across all stem cell disciplines.

The UK National Stem Cell Network acts as a network of the existing regional stem cell networks in the UK, to bring coordination and coherence to a range of national and regional activities in the field of stem cell research.

The UKNSCN secretariat receives financial support from four of the UK Research Councils:
Biotechnology and Biological Sciences Research Council (BBSRC)

Economic and Social Research Council (ESRC)

Engineering and Physical Sciences Research Council (EPSRC)

Medical Research Council (MRC)

The Network represents the UK stem cell research community and is run through an independent Steering Committee. Initially, the secretariat is operated by BBSRC on behalf of all the Government sponsors of stem cell research, including the Research Councils, the Department of Health and the Department for Innovation, Universities and Skills.

Source: Matt Goode

Biotechnology and Biological Sciences Research Council

Activity The Key To Managing Arthritis

2011-06-26T22:30:00.000-07:00

"University of Queensland" researchers have shown for the first time older women who exercise are more likely to not get stiff or painful joints.

The landmark study, published in the journal Arthritis Research & Therapy, shows women in their 70s could avoid the pain of arthritis by keeping active.

Dr Kristi Heesch, Dr Yvette Miller and Professor Wendy Brown from UQ's "School of Human Movement Studies" , have used data collected over three years as part of the Australian Longitudinal Study on Women's Health, targeting middle-aged and older women who had no symptoms of arthritis.

"What we found is if women in their 70s can do as little as 75 minutes of moderate physical activity a week, they will lessen their chances of developing frequent arthritis symptoms for three years," Dr Heesch said.

"The results also suggest that engaging in at least 150 minutes of moderate-intensity physical activity per week may be even more protective.

"Our results are the first to show a dose - response relationship between physical activity and arthritis symptoms in older women."

Dr Heesch said arthritis was a debilitating health problem, which is more likely to strike as people got older and affects more women than men.

"Arthritis is almost as common as cardiovascular disease in Australia, affecting 17 percent of the population," she said.

"If preventive intervention strategies, such as increasing physical activity participation by even small amounts, could delay the onset and development of symptoms of arthritis, there could be considerable cost savings to the healthcare system and to older women themselves, not to mention reductions in pain and suffering caused by this often debilitating health problem.

She said the study also looked at middle-aged women but there seemed to be no similar advantage in women of that age.

"We were surprised to find such a difference between middle-aged and older women," she said.

"One explanation is that occupational physical activity was not included in our assessment of physical activity and that many women in the mid-age cohort of the study were in paid work, whereas the older women were not."

Dr Heesch said her team is doing further research into the link between physical activity and self-reported diagnosis or treatment for arthritis.

uq.au

Tocilizumab Provides Significant Clinical Benefit In Rheumatoid Arthritis Patients

2011-06-25T22:15:00.000-07:00

The investigational compound tocilizumab (ActemraTM) significantly reduces disease activity in patients with moderate to severe rheumatoid arthritis (RA) who have an inadequate response to methotrexate, researchers announced at the European League Against Rheumatism (EULAR) 2007.

Josef Smolen, MD, chairman of the rheumatology department at the Medical University of Vienna, reported findings in 623 patients who had been randomized to receive tocilizumab 8 mg/kg, tocilizumab 4 mg/kg, or placebo, administered by intravenous infusion every four weeks. Tocilizumab is a novel monoclonal antibody targeting interleukin (IL)-6 signaling.

All patients enrolled in the study had moderate to severe active RA despite long- term metrotrexate treatment.

Participants in the trial continued to receive concomitant oral or parenteral methotrexate at their pre-study dose of 10 to 25 mg weekly throughout the trial and stopped all other disease-modifying anti-rheumatic drugs upon entry into the study.

The primary endpoint was the proportion of patients achieving American College of Rheumatology (ACR) 20 response at 24 weeks.

Results of the phase III tOcilizumab Pivotal Trial in methotrexate Inadequate respONders (OPTION) trial showed that 58.5% of patients in the 8 mg/kg group and 47.9% in the 4 mg/kg group achieved ACR20 responses at week 24 compared with 26.5% in the placebo group.

Also, 22% who received tocilizumab 8 mg/kg achieved ACR70, and 43.9% achieved ACR50. Only 2% of the placebo cohort achieved ACR70, and 10.8% achieved ACR50.

The analysis also showed a decrease in the Disease Activity Score in 28 joints (DAS28) starting the second week. At 24 weeks, the mean DAS28 score was reduced by 3.43 in the 8 mg/kg tocilizumab group, 2.63 in the 4 mg/kg tocilizumab group, and 1.55 in the placebo group.

Both doses of tocilizumab were generally well tolerated, and there was a similar rate of adverse events in the three study groups. The incidence of infections was slightly higher than with placebo but no incidence of tuberculosis was observed.

"Overall, the results show that tocilizumab in combination with methotrexate provides rapid and significant improvements in the signs and symptoms of RA," Dr. Smolen said.

He added that the high efficacy of Il-6 receptor inhibition with tocilizumab confirms the critical role of Il-6 in the pathophysiology of RA.

By Jill Stein

Jillstein03cs

Double Trouble For Rheumatoid Arthritis Patients: PLC-gamma-2 Regulates Osteoclastogenesis And B Cell Differentiation

2011-06-24T22:00:00.000-07:00

Rheumatoid arthritis (RA) is best known as a chronic inflammatory disease caused by the immune system inappropriately attacking the joints. However, the autoimmune response also leads to the recruitment and/or differentiation of cells known as osteoclasts -- which are cells that degrade and resorb bone. Current treatments for patients with RA target either the joint-specific immune response or the osteoclast-mediated bone erosion.

Now, in a study appearing online on October 19 in advance of publication in the November print issue of the Journal of Clinical Investigation, researchers from Washington University have shown that the protein PLC-gamma-2, which was already known to regulate the differentiation of B cells (one of the immune cells crucial to the autoimmune response seen in RA), is required for normal osteoclast development and function in mice. Roberta Faccio and colleagues therefore suggest that targeting PLC-gamma-2 might lead to control of both the immune-mediated joint destruction and osteoclast-mediated bone erosion seen in RA.

TITLE: PLC-gamma-2 regulates osteoclastogenesis via its interaction with ITAM proteins and GAB2

AUTHOR CONTACT:

Roberta Faccio

Washington University School of Medicine, St. Louis, Missouri, USA.

Contact: Karen Honey

Journal of Clinical Investigation

Vioxx Heart Risk Persists One Year After Stopping Use

2011-06-23T21:45:00.000-07:00

A new international study found that Merck's pain killer Vioxx (rofecoxib), which the drug company voluntarily withdrew from the market in 2004, found
that a near two-fold increased risk of heart, stroke and death persisted for up to one year after stopping use.

The study was the work of Dr Robert Bresalier, a professor of medicine at the MD Anderson Cancer Center in Houston, Texas, and colleagues from other research
centres in the US, Canada, Spain and the UK, is published in the 14 October 2008 issue of The Lancet.

In this latest study, Bresalier and colleagues found that the "risk was increased close to twofold, and the risk persisted for approximately a year",
according to a statement reported in the Washington Post.

But, "the good news is that, after a year, the risk seemed to go back down toward normal," Bresalier told the press.

Vioxx (rofecoxib) is a type of non-steroidal anti-inflammatory drug (NSAID). Specifically, it is a cox-2 inhibitor that targets an enzyme involved in
inflammation, the cyclooxygenase 2 (cox-2) enzyme. It was approved by the US Food and Drug Administration in 1999 for the treatment of osteoarthritis, acute
pain conditions, and dysmenorrhoea. But in 2004, Merck withdrew it because of concerns about raised risk of heart attack, stroke and death.

Other less targeted NSAIDs include ibuprofen and naproxen.

Bresalier said that he and other experts believed that all non-aspirin NSAIDs raised the risk of cardiovascular events.

"In fact, it seems to be a class effect for most if not all NSAIDs," said Bresaliers, adding that:

"There is a dose-dependent risk with Celebrex [an NSAID made by Pfizer] as well, whose magnitude was not that much different from Vioxx."

For the study, Bresalier and colleagues followed up participants who took part in the international trial APPROVe that compared Vioxx to placebo for 3 years.
APPROVe was a multicentre, randomized, placebo controlled, double blind trial involving nearly 2,600 patients with a history of colorectal adenomas (growths
or polyps in the colon) who were recruited at 108 centres worldwide during 2000 and 2001.

APPROVe, which was designed to see if Vioxx could reduce the recurrence of colon growths or polyps, was stopped in 2004 because of increased risk of heart
attack and stroke. But Bresalier and colleagues were able to get in touch with 84 per cent of the participants and follow their progress for another year
after their treatment stopped.

The analysis looked for the combined incidence of "non-fatal myocardial infarction, non-fatal stroke, and death from cardiovascular, haemorrhagic, and
unknown causes", wrote the authors.

The results showed that a year after they stopped using Vioxx, the participants still carried a 79 per cent higher risk of heart attack, stroke or death
compared to the participants who had been on placebo during the 3 year trial.

The risk of heart attack or stroke for participants on Vioxx during the trial was double that of the participants on placebo for up to year after the trial,
while the risk of death was up by 31 per cent compared to placebo.

Bresalier and colleagues said this was consistent with the increased risk observed in the trial, where the risk of having a cardiovascular event for the
participants taking Vioxx was double that of participants taking placebo.

Merck said in a statement reported by Reuters that:

"Using limited data from a prematurely terminated study needs to be interpreted very cautiously and in the context of the rest of the data from the extensive
clinical development program for Vioxx."

Bresalier and colleagues did find that Vioxx reduced the incidence of colon polyps.

Speaking to the press about NSAIDs, Bresalier said for people taking them only intermittently, for short term pain relief for example, the risk would most
likely be very small. Taking one or two pills is not going likely to give you a heart attack, and for the majority of people taking NSAIDs, they are safe
and effective. But you need to be more careful about taking high doses over a long period:

"If you have a history of cardiovascular disease, speak to your doctor to understand the relative risks and benefits. If you're somebody who really needs to
take these drugs because of chronic pain or severe arthritis, be aware of the issues. But you shouldn't be afraid to take these drugs if you need them," said
Bresalier, according to the Washington Post.

"Cardiovascular events associated with rofecoxib: final analysis of the APPROVe trial."

John A Baron, Robert S Sandler, Robert S Bresalier, Angel Lanas, Dion G Morton, Robert Riddell, Erik R Iverson, and David L DeMets.

The Lancet Early Online Publication, 14 October 2008.

DOI:10.1016/S0140-6736(08)61490-7

Click here for
Abstract.

Source: Journal Abstract, Washington Post, Reuters.

Written by: , PhD.

View drug information on Vioxx.

Emisphere Announces Recruitment Phase III Study For Oral Osteoarthritis Treatment

2011-06-22T21:30:00.000-07:00

Emisphere
Technologies, Inc. (Nasdaq: EMIS) announced that Novartis Pharma AG
and Nordic Bioscience have completed recruitment for a multi-center Phase
III study exploring the safety and efficacy of an oral formulation of
salmon calcitonin using Emisphere's proprietary Eligen Technology to treat
patients with osteoarthritis of the knee. This study, which will be used to
support the filing with health authorities worldwide, includes more than
1,100 patients between 51 and 80 years old with a medical history and
symptoms of knee osteoarthritis. The study will be conducted mainly in
Europe and is estimated to complete second half 2010.

Osteoarthritis ("OA") is a clinical syndrome in which low-grade
inflammation results in joint pain, caused by a wearing-away of cartilage
that cushions the joints and the destruction or decrease of synovial fluid
that lubricates those joints. As OA progresses, pain can result when the
patient bears weight upon the joints, including walking and standing. OA is
the most common form of arthritis, and affects nearly 21 million people in
the United States, accounting for 25% of visits to primary care physicians,
and half of all non-steroidal anti-inflammatory drug prescriptions. It is
estimated that 80% of the population will have radiographic evidence of OA
by age 65.

"The problems associated with osteoarthritis will escalate as the
population ages," said Michael V. Novinski, President and Chief Executive
Officer of Emisphere. "This Phase III study aims at demonstrating that oral
salmon calcitonin, in combination with our Eligen drug delivery technology,
may contribute to solving this problem, and also shows that Emisphere is a
valuable partner in drug development."

About Emisphere Technologies, Inc.

Emisphere is a biopharmaceutical company that focuses on a unique and
improved delivery of therapeutic molecules using its Eligen Technology.
These molecules and compounds could be currently available or in
development. Such molecules are usually delivered by injection; in many
cases, their benefits are limited due to poor bioavailability, slow on-set
of action or variable absorption. The Eligen Technology can be applied to
the oral route of administration as well other delivery pathways, such as
buccal, rectal, inhalation, intra-vaginal or transdermal. The website is:
emisphere.

Safe Harbor Statement Regarding Forward-looking Statements

The statements in this release and oral statements made by
representatives of Emisphere relating to matters that are not historical
facts (including without limitation those regarding the timing or potential
outcomes of research collaborations or clinical trials, any market that
might develop for any of Emisphere's product candidates and the sufficiency
of Emisphere's cash and other capital resources) are forward-looking
statements that involve risks and uncertainties, including, but not limited
to, the likelihood that future research will prove successful, the
likelihood that any product in the research pipeline will receive
regulatory approval in the United States or abroad, the ability of
Emisphere and/or its partners to develop, manufacture and commercialize
products using Emisphere's drug delivery technology, Emisphere's ability to
fund such efforts with or without partners, and other risks and
uncertainties detailed in Emisphere's filings with the Securities and
Exchange Commission, including those factors discussed under the caption
"Risk Factors" in Emisphere's Annual Report on Form 10-K (file no. 1-10615)
filed on March 13, 2008 and our Quarterly Report on Form 10-Q for the
quarter ended June 30, 2008, filed on August 11, 2008.

Emisphere Technologies, Inc

emisphere

Potential Fix For Damaged Knees Identified By Study

2011-06-21T21:15:00.000-07:00

Investigators from Hospital for Special Surgery have shown that a biodegradable scaffold or plug can be used to treat patients with damaged knee cartilage. The study is unique in that it used serial magnetic resonance imaging (MRI) and newer quantitative T2 mapping to examine how the plug incorporated itself into the knee. The research, abstract 8372, was presented during the annual meeting of the American Orthopedic Society for Sports Medicine, June 9-12, in Keystone, Colo.

"The data has been encouraging to support further evaluation of this synthetic scaffold as a cartilage repair technique," said Asheesh Bedi, M.D., a fellow in sports medicine and shoulder surgery at Hospital for Special Surgery who was involved with the study. Dr. Bedi performed analysis of MRI scans of patients primarily treated by Riley Williams, M.D., director of the Institute for Cartilage Repair at Hospital for Special Surgery. "The Trufit plug has been designed to have mechanical properties that are similar to cartilage and bone," Dr. Bedi said.

Damage to so-called articular cartilage can occur in various ways, ranging from direct trauma in a motor vehicle accident to a noncontact, pivoting event on the soccer field. "Articular cartilage lacks the intrinsic properties of healing - you are essentially born with the articular cartilage that you have," Dr. Bedi said. Left untreated, these injuries can increase loads placed on the remaining intact cartilage and increase the risk of progression to degenerative arthritis. One way to treat patients with symptomatic chondral lesions is an OATS procedure, in which cartilage is transferred from one portion of the knee to treat another. Because this is a "robbing Peter to pay Paul" situation, researchers at Hospital for Special Surgery set out to examine whether they could use a biodegradable plug, the Trufit CB plug, to fill the donor site. The goal was to monitor how the plug incorporated itself into the knee and to evaluate the quality of the repair cartilage.

The Trufit plug has two layers. The top layer has properties similar to cartilage and the lower layer has properties similar to bone. The bilayered structure has mechanical properties that approximately match the adjacent cartilage and bone. Surgeons inserted the plug in the knees of 26 patients with donor lesions from OATS procedures and followed up with imaging studies (with MRI and T2-mapping) at various intervals for a period of 39 months.

"Quantitative MRI, when combined with morphologic assessment, allows us to understand the natural history of these repair techniques and define those patients who are most likely to benefit from the surgery," said Hollis Potter, M.D., chief of the Division of Magnetic Resonance Imaging, director of Research in the Department of Radiology and Imaging at Hospital for Special Surgery and lead author of the study. "We gain knowledge about the biology of integration with the host tissue, as well as the repair tissue biochemistry, all by a noninvasive imaging technique."

"What we found was that the plug demonstrated a predictable process of maturation on imaging studies that paralleled the biology of their incorporation," Dr. Bedi said. "With increasing postoperative duration, the repair tissue demonstrated encouraging properties with T2-values that resembled native articular cartilage."

Dr. Williams, Dr. Bedi and other surgeons at Hospital for Special Surgery are involved in ongoing studies to investigate the efficacy of the TruFit plug in treating primary cartilage defects as well. "What is unique about this study is that we have serial MRI with T2 mapping at various time points after surgery, which allows us to really examine the natural history of plug incorporation," Dr. Bedi said.

Dr. Williams believes that there is a role for scaffold-based cartilage repair strategies in the treatment of symptomatic cartilage lesions. "It is our hope that we can successfully treat these cartilage problems over the long term, thus restoring normal knee function and slowing the progression of knee arthritis," Dr. Williams said.

Other authors involved in the study are Li Foong Foo, M.D., and the Cartilage Study Group.

Source:
Phyllis Fisher

Hospital for Special Surgery

European Medicines Agency Recommends Restricted Use For Piroxicam

2011-06-20T21:00:00.000-07:00

The European Medicines Agency (EMEA) has recommended restrictions on the
use of piroxicam-containing medicinal products because of the risk of
gastrointestinal side effects and serious skin reactions. The Agency's
Committee for Medicinal Products for Human Use (CHMP) concluded that
piroxicam should no longer be used for treatment of short-term painful
and inflammatory conditions. Piroxicam can still be prescribed for the
symptomatic relief of osteoarthritis, rheumatoid arthritis and
ankylosing spondylitis. However it should not be the first choice of
non-steroidal anti-inflammatory drug (NSAID) treatment in these
conditions.

Prescription of piroxicam should always be initiated by a physician
experienced in the treatment of patients with inflammatory or
degenerative rheumatic diseases and treatment should be used in the
lowest dose (no more than 20 mg per day) and for the shortest duration
possible. In any case, the treatment should be reviewed after the first
14 days of starting.

In addition, the CHMP recommended new contraindications and strengthened
warnings for piroxicam, further details of which are provided in a
separate question-and-answer document.

Topical medicines containing piroxicam are not concerned by these
restrictions.

Further to the request of the European Commission, the CHMP initiated a
full assessment of the benefits and risks of piroxicam in September
2006, because a review of non-selective NSAIDs showed that piroxicam
could be associated with a higher risk of gastrointestinal side effects
and serious skin reactions than other non-selective NSAIDs.

The CHMP recommendations will now be forwarded to the European
Commission for adoption of a legally binding decision, applicable in all
EU Member States.

1. The safety review was conducted in accordance with Article 31 of
the Community code on human medicinal products (Directive 2001/83/EC as
amended).

2. More information about the recommendations for piroxicam is
available in a separate question- and-answer document here
here.

3. A press release announcing the start of the procedure for
piroxicam can be found
here.

4. More information about the review of NSAIDs can be found
here.

5. This press release, together with other information about the
work of the EMEA, may be found on the EMEA website:

European Medicines Agency (EMEA)

Lupus More Severe In Patients With Southern European Ancestry

2011-06-19T20:45:00.000-07:00

Systemic lupus erythematosus (SLE) patients with a higher percentage of ancestry from southern Europe have more severe disease manifestations, according to new research presented at EULAR 2008, the Annual Congress of the European League Against Rheumatism in Paris, France.

According to the results of the research, northern European ancestry is shown to be associated with the relatively milder mucocutaneous (skin) manifestations of SLE, whereas southern European ancestry contributes to more severe manifestations of the disorder such as nephritis (inflammation of the kidneys) and increased production of specific autoantibodies (antibodies that fail to recognise and therefore attack the body's own cells, tissues or organs).

SLE is a complex autoimmune disease characterised by chronic inflammation and damage to body tissues, which occurs as a result of the production of abnormal antibodies that target and cause damage to cells of the patient's body, including immune cells. SLE has the potential to affect a variety of areas of the body, including the heart, lungs, kidneys, joints, and/or nervous system. The course of the disease is unpredictable, with periods of illness (called flares) alternating with remission. Lupus can occur at any age but is most common in women, particularly of non-European descent. Until now, the relationship between specific European ancestry and SLE severity has not been studied.

Professor Lindsey A Criswell of the University of California, San Francisco, USA, who led the study, said: "Exploring the ancestry and genetic make-up of patients in relation to their disease today helps us to better understand the complex nature of SLE and why it manifests itself differently in different people. This study shows a clear correlation between specific European ancestry and SLE disease severity and autoantibody production, which may further assist in understanding the risk factors for this condition and should help us better understand and manage this disease in the future."

Researchers in this study examined 1,270 SLE patients from four independent cohorts who had at least 90% European ancestry according to continental ancestry-informative genetic markers. 1,409 genome-wide markers informative for northern versus southern European ancestry were then analysed to estimate the percentage of northern European ancestry for each subject using the STRUCTURE programme. The association between northern European ancestry and specific SLE subphenotypes, including autoantibody production, nephritis, arthritis and mucocutaneous manifestations was then explored.

Northern European ancestry was positively associated with photosensitivity (odds ratio=2.0, p

Abstract number: AB0147

About EULAR
The European League Against Rheumatism (EULAR) is the organisation which represents the patient, health professional and scientific societies of rheumatology of all the European nations.

The aims of EULAR are to reduce the burden of rheumatic diseases on the individual and society and to improve the treatment, prevention and rehabilitation of musculoskeletal diseases. To this end, EULAR fosters excellence in education and research in the field of rheumatology. It promotes the translation of research advances into daily care and fights for the recognition of the needs of people with musculoskeletal diseases by the governing bodies in Europe.

Diseases of bones and joints, such as rheumatoid arthritis and osteoarthritis cause disability in 4 - 5 % of the adult population and are predicted to rise as people live longer.

As new treatments emerge and cellular mechanisms are discovered, EULAR 2008 brings together more than 12,000 experts - scientists, clinicians, healthcare workers, pharmaceutical companies and patients - to share their knowledge in a global endeavour to challenge the pain and disability caused by musculo-skeletal disorders.

To find out more information about the activities of EULAR, visit: eular/

Source: Rory Berrie / Camilla Dormer

European League Against Rheumatism

Patients With Rheumatoid Arthritis Benefit From Gene Therapy

2011-06-18T20:30:00.000-07:00

Researchers have reported the first clinical evidence that gene therapy reduces symptoms in patients with rheumatoid arthritis, an important milestone for this promising treatment which has endured a sometimes turbulent past. Described in the February issue of the journal Human Gene Therapy the findings stem from a study of two patients with severe rheumatoid arthritis conducted in Germany and led by an investigator at Beth Israel Deaconess Medical Center (BIDMC).

Originally conceived as a means of treating genetic diseases, such as cystic fibrosis and hemophilia, gene therapy involves implanting a normal gene to compensate for a defective gene in the patient. The first clinical trial to test gene therapy was launched in 1990 for the treatment of a rare, genetic immunodeficiency disease.

"This study helps extend gene therapy research to nongenetic, nonlethal diseases," explains principal investigator Christopher Evans, PhD, Director of the Center for Advanced Orthopaedic Studies at BIDMC. "Rheumatoid arthritis [RA] is an extremely painful condition affecting multiple joints throughout the body. Arthritis is a good target for this treatment because the joint is a closed space into which we can inject genes," adds Evans, who is also the Maurice Muller Professor of Orthopaedic Surgery at Harvard Medical School.

A classic autoimmune disease, RA develops when, for unknown reasons, the body's immune system turns against itself, causing joints to become swollen and inflamed. If the disease is inadequately controlled, the tissues of the joint are eventually destroyed. Although anti-inflammatory agents and biologics can help to mitigate symptoms, there is no cure for the condition, estimated to affect more than 2 million individuals in the U.S. alone.

Evans has spent many years studying the molecules responsible for the breakdown of cartilage in patients with arthritis, identifying interleukin-1 as a good target. But, he adds, once he had this answer, another question was not far behind: How could he effectively reach the joints to block the actions of this protein?

Gene therapy provided the answer.

By implanting a gene in the affected joint, he was able to stimulate production of a human interleukin-1 receptor antagonist protein, which serves to block actions of the interleukin-1 protein.

"The idea is that by remaining in place, the new gene can continuously block the action of the interleukin-1 within the joints," says Evans. "In essence, the gene becomes its own little factory, continuously working to alleviate pain and swelling."

In 2005, in a study published in the Proceedings of the National Academy of Sciences (PNAS), Evans and colleagues demonstrated that the IL-1Ra gene could be safely transferred to human joints in patients with RA. In this new paper, the authors aimed to prove that the therapy was not only safe, but that it was of therapeutic benefit.

Two study subjects were recruited. (The number reduced from six study subjects following severe adverse events in an unrelated gene therapy trial taking place elsewhere, according to Evans.) Both subjects were postmenopausal females under the age of 75 with a diagnosis of advanced rheumatoid arthritis. After tissue was removed from the subjects' knuckle joints, a harmless retrovirus was inserted into the tissue cells, in order to serve as a "vector" to transport the gene into the patients' joints. After being placed in culture to grow and replicate, the cells were injected back into the afflicted joints.

After four weeks, patients reported reduced pain and swelling, according to Evans. "In one of the two subjects, these effects were dramatic, and the gene-treated joints remained pain-free even though other joints experience flares." Subsequent laboratory tests showed that tissues removed from the subject's joint tissue synthesized lower amounts of disease-related proteins, confirming that the reduction in pain and swelling resulted from the actions of the implanted gene.

"Existing treatments for rheumatoid arthritis are costly and need to be administered regularly," says Evans, adding that in addition to risk of side effects, not all patients respond well. "This paper provides us with the first real evidence that painful symptoms can indeed be lessened through gene therapy."

Ongoing work will focus on the use of gene therapy for the treatment of osteoarthritis, as well as rheumatoid arthritis.

This study was funded, in part, by grants from the National Institutes of Health and Orthogen, a German biotechnology company.

Study coauthors include Peter Wehling, Julio Reinecke, Axel Baltzer, Marcus Granrath, Klaus Schulitz, Carl Schultz, and Rudiger Krauspe of the University of Dusseldorf School of Medicine, Germany; Theresa Whiteside, Elaine Elder and Paul Robbins of the University of Pittsburgh School of Medicine; and Steven Ghivizzani of the University of Florida College of Medicine.

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks in the top four in National Institutes of Health funding among independent hospitals nationwide. BIDMC is clinically affiliated with the Joslin Diabetes Center and is a research partner of the Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox. For more information, visit bidmc.

Source: Bonnie Prescott

Beth Israel Deaconess Medical Center

Novel Drugs Selectively Target Pathway Important In Rheumatoid Arthritis

2011-06-17T20:15:00.000-07:00

Methotrexate (MTX), a folate antagonist that blocks folic acid activity, is the most widely used disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis. It enters the cell via several pathways, one of which involves folate receptor ?? (FR??), which is highly specific for cells present in the joints of patients with rheumatoid arthritis (RA). During the last two decades, a second generation of folate antagonists has been designed to address some of the limitations of MTX, which include adverse side effects and resistance. A new study examined the capacity of several of these new drugs to determine whether they could selectively target cells that express FR??. The study was published in the January issue of Arthritis & Rheumatism (www3.interscience.wiley/journal/76509746/home).

Led by Gerrit Jansen of the VU University Medical Center in Amsterdam, researchers analyzed FR?? expression from biopsy samples from the knee joints of RA patients before and after four months of treatment with MTX and from controls. These experiments confirmed that FR?? expression is highly specific to activated macrophages (a type of immune cell that plays a role in the inflammatory response in RA) in the synovial membrane of RA patients.

The researchers went on to examine new folate antagonists to determine which ones would most likely be beneficial in treating synovial inflammation. Several of these agents showed a markedly higher binding affinity for FR?? compared to MTX, which has a high affinity for entering cells via another pathway known as reduced folate carrier (RFC). This pathway is found throughout the body, however, and is therefore not specific for synovial cells. Researchers also examined whether two of the newer drugs would inhibit growth of FR??-expressing cells and found that one of them, BCG 945, accomplished this at low concentrations. Interestingly, the uptake of BCG 945 was inhibited by the addition of folic acid. "In this context, it may be anticipated that, for example, fortification of food with folate may reduce the activity of this folate antagonist, whereas restriction in dietary folate intake could further enhance the therapeutic efficacy of these types of drugs," the authors state. BGC 945 was originally discovered at the Institute of Cancer Research in London, and is now known as ONX 0801. Onyx Pharmaceuticals has an exclusive worldwide license to this compound.

They note that although MTX is the drug of first choice in the treatment of RA, its efficacy can be improved. "Further evaluation of folate antagonists with properties of high binding affinity for FR?? and low affinity for the RFC may pave the road for a more selective targeted therapy of activated synovial macrophages," they conclude.

In an accompanying editorial in the same issue, Christoph Fiehn of the Center for Rheumatic Diseases in Germany notes that folate antagonists remain the key to RA treatment, both now and in the future. "Antifolate drugs that, unlike MTX, are FR??-specific would have a stronger effect on synovial macrophages and a weaker effect on other types of cells that take up MTX by the ubiquitously expressed RFC," he explains. "A higher therapeutic effect and a lower rate of side effects of FR??-specific antifolates as compared with MTX could possibly be the result."

Articles: "Folate Receptor ?? as a Potential Delivery Route for Novel Folate Antagonists to Macrophages in the Synovial Tissue of Rheumatoid Arthritis Patients," Joost W. van der Heijden, Ruud Oerlemans, Ben A.C. Dijkmans, Huiling Qi, Conny J. van der Laken, Willem F. Lems, Ann L. Jackman, Maarten C. Kraan, Paul P. Tak, Manohar Ratnam, Gerrit Jansen, Arthritis & Rheumatism, January 2009; 60:1; pp.12-21.

"The Future of Folic Acid Antagonist Therapy in Rheumatoid Arthritis," Christoph Fiehn, Arthritis & Rheumatism, January 2009; 60:1; pp. 1-4.

Source: Sean Wagner

Wiley-Blackwell

Genetic Connection Found Between Short Stature And Arthritis

2011-06-16T20:00:00.000-07:00

Common genetic variants linked to arthritis may also play a role in human height, a new study shows.

The international study was co-led by the University of Michigan School of Public Health. The journal Nature Genetics published the findings online Jan. 13.

The new study confirms observations by health professionals of a connection between decreased height and increased risk of osteoarthritis, the most common form of arthritis. Researchers speculate that both extremes of height may be associated with osteoarthritis for different reasons. Shorter bones and/or less cartilage may render the joints more susceptible to damage, while longer bones may produce greater levels of damaging stress on the joints.

The findings are exciting for several reasons, said Gon?§alo Abecasis, assistant professor in the School of Public Health. For one, there are many genes that control height, but only a few associated with osteoarthritis, he said.

"In this case the gene we picked also is important in osteoarthritis and it's actually quite hard to find genes for osteoarthritis," said Abecasis, who co-directed the study with Karen Mohlke of the University of North Carolina. "One of the things we were excited about is you could study (height) in many people, and once you've done that you have a short list of genes that you can then study for what they do in terms of osteoarthritis."

The findings also add to the general understanding of height.

"It is useful to know all genes responsible for height variation, so we are reassured if our baby is shorter than others because he has a collection of "short" alleles on his DNA, and not because he has something wrong, like a metabolism disorder," said Serena Sanna, co-author who worked on the paper as a post-doctoral student in Abecasis' group and who is now at the National Research Council di Cagliari in Italy. Anne Jackson, a research specialist at U-M, is also a co-author.

To arrive at their findings, researchers from the United States and Europe analyzed the genomes of more than 35,000 people. If there were average height differences for individuals with certain genetic variants, this indicated that something in that genomic region containing the variants likely influenced height. In this particular study, researchers initially examined the effects of more than 2 million genetic variants.

The new variant accounts for less than 1 percent of the genetic basis of height, and is associated with an average difference in height of about 0.4 centimeters, or a little more than an eighth of an inch. The range went from 0.3 cm to 1.4 cm, depending on the population and whether an individual had one or two copies of the so-called taller version of the variant. A variety of factors, including genetics, diet and prenatal environment, interact to determine how tall someone grows. It is currently thought that genetic factors are responsible for at least 80 percent of the variation in height among people.

The variants most strongly associated with height lie in a region of the human genome thought to influence expression of a gene for growth differentiation factor 5, called GDF5, which is a protein involved in the development of cartilage in the legs and other long bones. Rare variants in the GDF5 gene have been associated with disorders of skeletal development, and more common variants recently have been tied to susceptibility to osteoarthritis of the hip and knees in Asian and European populations.

The completion of the map of human genetic variation, or HapMap, has fueled a surge in this type of genome-wide association study, with most of the growth coming in the past 10 months. Researchers around the globe have now associated more than 60 common DNA variants with the risk of more than 20 common diseases or related traits.

The research received major support from National Human Genome Research Institute, National Institute on Aging, National Institute of Diabetes and Digestive and Kidney Diseases, and the National Heart, Lung and Blood Institute, all of which are part of the National Institutes of Health.

For more on Abecasis, visit: sph.umich/csg/abecasis/.

For more on the School of Public Health, visit: sph.umich/.

The University of Michigan School of Public Health has been working to promote health and prevent disease since 1941, and is consistently ranked among the top five public health schools in the nation. Faculty and students in the school's five academic departments and dozens of collaborative centers and initiatives are forging new solutions to the complex health challenges of today, including chronic disease, health care quality and finance, emerging genetic technologies, climate change, socioeconomic inequalities and their impact on health, infectious disease and the globalization of health. Whether making new discoveries in the lab or researching and educating in the field, our faculty, students and alumni are deployed around the globe to promote and protect our health.

Source: Laura Bailey

University of Michigan

Evidence Of Benefit Lacking For Many Common Ways Of Treating Osteoarthritis Of The Knee

2011-06-15T19:45:00.000-07:00

A new scientific review released by HHS' Agency for Healthcare Research and Quality concludes that evidence of benefit is lacking for many common ways of treating osteoarthritis of the knee, including popular dietary supplement ingredients, a common surgical procedure, and injected preparations.

The review found that glucosamine and chondroitin, over-the-counter dietary supplement ingredients that are used widely because of their purported benefits to relieve knee pain caused by osteoarthritis and improve physical functioning, appear to be no more effective than placebos. A placebo is a harmless substance given to selected patients in a clinical trial that looks like the real drug or injection being studied, but which has no medical effect.

The review, which was requested and funded by HHS' Centers for Disease Control and Prevention, also failed to find convincing evidence of benefit from arthroscopic surgery to clean the knee joint with or without removal of debris and loose cartilage.

Published studies generally report that injections with hyaluronan preparations (substances that are intended to improve lubrication of the knee joint) improve scores on patient questionnaires used to measure pain and function. However, the evidence is uncertain because of variation in study quality and difficulty determining whether changes in scores translate into real clinical improvements for patients.

"Millions of Americans seek relief from the pain and reduced mobility caused by osteoarthritis of the knee," said AHRQ Director Carolyn M. Clancy, M.D. "However, they should work with their clinicians to decide the best course of treatment for them based on what has and has not been proven to work."

Osteoarthritis is a widespread, costly disease that wears away the cartilage cushioning the knee joint, causing pain and reducing mobility. Arthritic diseases, which include osteoarthritis, affect an estimated 46 million people in the United States, and at age 64 and older, one in 10 Americans is estimated to have osteoarthritis of the knee. Osteoarthritis and related arthritic conditions cost more than $81 billion a year in medical care, lost wages, and other expenses.

The authors, who were led by David J. Samson, M.S., associate director of the AHRQ-supported Blue Cross and Blue Shield Association Evidence-based Practice Center in Chicago, reviewed findings from 53 randomized clinical trials of glucosamine, chrondroitin, and injections with hyaluronan preparations and 23 studies of arthroscopy. The review scrutinized individual studies concerned with these treatments' effects as well as meta-analyses that analyzed the combined evidence of groups of studies.

According to authors, better quality randomized clinical trials are needed to clarify whether these treatments are beneficial. However, given the aging of the population and increasing prevalence of obesity - both risk factors for osteoarthritis of the knee - "research on new approaches to prevention and treatment of osteoarthritis of the knee should be a high priority."

For a copy of Treatment of Primary and Secondary Osteoarthritis of the Knee, click here.

ahrq

FDA Approves Monthly Injectable Drug For Treating Three Types Of Immune-Related Arthritis

2011-06-14T19:30:00.000-07:00

The U.S. Food and Drug Administration today approved Simponi (golimumab), a monthly treatment for adults with moderate-to-severe rheumatoid arthritis, active psoriatic arthritis, and active ankylosing spondylitis.

All three conditions are chronic disorders in which the immune system attacks multiple joints, causing stiffness, pain, and restricted motion.

"Today's approval provides another treatment option for patients with these three debilitating disorders," said Bob Rappaport, M.D., director of the Division of Anesthesia, Analgesia, and Rheumatology Products in the FDA's Center for Drug Evaluation and Research. "And the steps we're taking to minimize the risks will give patients the same level of safety protection required for other drugs in its class."

Simponi is injected under the skin. It is intended for use in combination with the immunosuppressant drug methotrexate in patients with rheumatoid arthritis. It also may be used with or without methotrexate for psoriatic arthritis and alone in patients with ankylosing spondylitis, a chronic inflammatory arthritis of the spine.

In clinical trials, patients who received Simponi for one of the three conditions showed improvements in the signs and symptoms common to their form of arthritis.

Simponi is in a class of drugs that target and neutralize tumor necrosis factor-alpha (TNF-?±), a protein that, when overproduced in the body due to chronic inflammatory diseases, can cause inflammation and damage to bones, cartilage and tissue. Like other TNF- ?± blockers, Simponi labeling includes a boxed warning alerting patients and health care professionals to the risk of tuberculosis and invasive fungal infections with use of the drug. The FDA also required a risk evaluation mitigation strategy (REMS) for Simponi, as it required for other TNF-?± blockers. The REMS for Simponi includes a Medication Guide for patients and a communication plan to help prescriber's understand the drug's risks.

The most common adverse reactions to Simponi include upper respiratory tract infection, sore throat and nasal congestion.

Simponi is marketed by Centocor Ortho Biotech Inc., Malvern, Pa.

Source
U.S. Food and Drug Administration

View drug information on Simponi.

Phase II Results For Low-Dose Oral Immune Tolerance Therapy (ARG201) In Systemic Scleroderma Published

2011-06-13T19:15:00.000-07:00

arGentis Pharmaceuticals, LLC announced that the Phase II results using highly purified type 1 bovine collagen orally (now known as ARG201) in the treatment of diffuse cutaneous systemic sclerosis (scleroderma - SSc) have been published in the June issue of Arthritis & Rheumatism, a major peer-reviewed rheumatology research journal. Systemic sclerosis is an autoimmune disease causing widespread fibrosis of the skin and internal organs. ARG201 is an immunotherapy that induces low dose oral immune tolerance in SSc patients causing downregulation of the body's autoimmune response. There are no approved treatments for the underlying cause of SSc, which has a median survival of eleven years (Mayes 2004).

The article entitled, "A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Oral Type I Collagen Treatment in Patients With Diffuse Cutaneous Systemic Sclerosis," reviews the results of the 168-patient, twelve center trial in which patients were administered a precise dose of highly purified type 1 collagen or placebo for 12 months with follow up at 15 months. Two prospectively subpopulations, Early Phase SSc patients (diagnosed for ?‰¤ 3 years) and Late Phase SSc patients (diagnosed from 3 to 10 years) were included in the trial due to differences in immunologic function of the two groups. The differences were borne out in the trial results. Late Phase patients had a statistically and clinically significant decrease from baseline in modified-Rodnan Skin Scores (-7.9 units) in the collagen treated patients versus the placebo group (-2.9 units). There was no difference in skin scores in Early Phase patients; although subsequent analysis demonstrated that patients who have been diagnosed as early as 1.75 years diagnosis may benefit from type 1 collagen therapy. The trial also demonstrated a high correlation between Late Phase patients who had significant changes in skin scores and that of other clinical outcomes. There were no adverse events in the trial attributed to the therapy.

Additionally, whether patients had at least 25% improvement in MRSS depended on whether they were Early or Late Phase patients at 12 months (p=0.014) and 15 months (p=0.031). A statistically significant upregulation of IL-10 (p=0.01), a marker for tolerance induction and a potent antifibrotic cytokine, was also seen in treated Late Phase SSc patients at 12 and 15 months.

"This trial delineated both clinically and immunologically the differences between Early Phase and Late Phase diffuse SSc patients," said Arnold E. Postlethwaite, principal investigator. "The reduction in skin scores among the Late Phase patients also demonstrates clinically meaningful improvement for the first time in a large, randomized trial in systemic sclerosis."

ARG201 has been granted orphan status by the U.S. Food and Drug Administration. Phase III trials will begin in the first half of 2009.

About Systemic Sclerosis

Systemic sclerosis (SSc or systemic scleroderma), a type of Scleroderma, is an autoimmune disease causing widespread fibrosis of the skin, lungs and other organs. As SSc progresses, patients suffer increasing difficulties with digestion, breathing, joint pain and often develop pulmonary hypertension. Median survival from diagnosis is eleven years (Mayes, 2004). There are approximately 80,000 SSc patients in the U.S. with similar numbers in the European Union. No therapies are presently available to treat the underlying cause of the disease.

About arGentis

arGentis Pharmaceuticals, LLC is a diversified specialty biopharmaceutical company seeking to license and commercialize therapies with demonstrated proof of concept for chronic diseases. Our pipeline consists of mid- and late-stage platform technologies in both autoimmunity and ophthalmology. ARG201, the company's lead compound for the treatment of systemic sclerosis, will enter Phase III trials in 2009. The ophthalmology pipeline includes three therapies for dry eye syndrome which are uniquely applied to the outer upper and lower eyelids for transdermal delivery to the affected glands.

arGentis Pharmaceuticals, LLC

Women With Osteoporosis Suffer More If They Have Previously Broken A Bone, Say Scientists

2011-06-12T19:00:00.000-07:00

Osteoporosis is more common in women who have fractured bones when they were younger - and they experience a similar loss in health-related quality of life as those with arthritis, lung disease, diabetes and other chronic diseases.

In an international study, led in the UK by scientists from the universities of Southampton and Cambridge, 60,000 women over the age of 55 were interviewed, 4079 of them British. The team found that 90 per cent of women with fractures suffered more mobility problems, pain, anxiety or depression.

Cyrus Cooper, professor of rheumatology at the Medical Research Council Lifecourse Epidemiology Unit, University of Southampton's Faculty of Medicine, comments: "Our study shows that the effects of fractures result in significant reductions in quality of life that are as lasting and as disabling as other chronic conditions. As important, the greater the number of fractures, the greater the disability. More needs to be done to more to identify and treat individuals at the highest risk of fractures."

Approximately 40 per cent of women over 50 will suffer a fracture; the most common sites are the hip, spine and wrist. These fractures often carry with them chronic pain, loss of independence, and especially in the case of hip fracture, an increased risk of death. Because the likelihood of fractures increases substantially with older age, fracture numbers are projected to rise as the population ages.

Using a standardized index measuring five dimensions of health (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression), the study authors administered health surveys to compare the overall health status, physical function and vitality of participants and assess health-related quality of life. The study found that spine, hip and upper leg fractures resulted in the greatest decrease in quality of life.

Study Details

The study is from the Global Longitudinal Study of Osteoporosis in Women (GLOW), which is led by the University of Massachusetts Medical School. It was published online, 15 July 2010, in the Mayo Clinic Proceedings.

The lead author of the paper is Jonathan D. Adachi, the Alliance for Better Bone Health Chair in Rheumatology at St. Joseph's Healthcare and McMaster University in Ontario.

GLOW is a prospective, international cohort study of women 55 years of age and older who visited their primary care physician during the 2 years prior to enrolment in the study. More than 60,000 women were recruited by more than 700 primary care physicians in 17 cities in 10 countries (Australia, Belgium, Canada, France, Germany, Italy, Netherlands, Spain, United Kingdom and United States). In GLOW, information is being gathered on fracture risk factors, treatments, life style characteristics, and fracture outcomes over a 5 year period.

GLOW in Southampton

25,300 European women are participating in GLOW. Professor Cyrus Cooper, professor of rheumatology, MRC Lifecourse Epidemiology Unit, based at Southampton General Hospital and Professor Juliet Compston, professor of bone medicine and honorary consultant physician at the University of Cambridge, School of Clinical Medicine, both co authors of this article, collaborated to enrol 4079 women from the Southampton area. Of these participants, 21 per cent had a previous fracture.

Source: Southampton University

Phase III ACTEMRA(TM) (tocilizumab) Study Results Demonstrate Significant Improvement In Signs And Symptoms Of Patients With Rheumatoid Arthritis

2011-06-11T18:45:00.000-07:00

Roche today announced that
results from the OPTION (TOcilizumab Pivotal Trial in Methotrexate
Inadequate respONders) trial, the first international Phase III study of
ACTEMRA(TM) outside of Japan, successfully met its primary endpoint in
patients with moderate to severe rheumatoid arthritis (RA) who had an
inadequate response to methotrexate, a current standard of care. The study
showed that a greater proportion of RA patients treated with ACTEMRA(TM)
(either 4mg/kg or 8mg/kg) plus methotrexate achieved a significant
improvement in disease signs and symptoms (ACR20) at week 24, compared with
placebo plus methotrexate.

The preliminary analysis demonstrated that the safety profile of
ACTEMRA(TM) was consistent with earlier development studies; the most
common side effects reported in the study were upper respiratory tract
infection and headache. There was a similar incidence of infection reported
across treatment arms.

"We are pleased that this study confirms the favorable activity of
ACTEMRA(TM) in the treatment of RA," said Lars Birgerson, MD, PhD, Vice
President, Medical Affairs, Roche. "Through its unique blockade of the
interleukin-6 receptor, ACTEMRA(TM) may offer a novel approach to reduce
the debilitating symptoms of RA and help patients who may not be achieving
sufficient relief from standard therapies like methotrexate."

Data from this trial will be submitted for presentation at upcoming
international scientific meetings. In addition, four other Phase III trials
exploring ACTEMRA(TM) in RA are ongoing with three of them scheduled to
report in 2007.

About the OPTION Study

The OPTION (TOcilizumab Pivotal Trial in Methotrexate Inadequate
respONders) study is a three-arm, randomized, double-blind, controlled
study designed to evaluate the safety and efficacy of ACTEMRA(TM) plus
methotrexate compared to placebo plus methotrexate in RA patients who had
an inadequate response to methotrexate alone. Patients received ACTEMRA(TM)
intravenously (either 4mg/kg or 8mg/kg) every 4 weeks plus methotrexate
weekly or placebo infusions plus methotrexate weekly. Patients' response
was measured using ACR, a standard assessment developed by the American
College of Rheumatology to measure the signs and symptoms of RA. A 20%
reduction in the signs and symptoms of RA is represented as ACR20. The
study enrolled 623 patients at 73 trial sites in 17 countries outside the
United States.

The OPTION study is one of five Phase III trials underway to study
ACTEMRA(TM) as a potential new treatment for RA. Roche and Chugai have
initiated the collaborative clinical development program that has enrolled
a total of more than 4,000 patients in 41 countries including the United
States and several European countries.

About ACTEMRA(TM) (tocilizumab)

ACTEMRA(TM) is the first humanized interleukin-6 (IL-6)
receptor-blocking monoclonal antibody with a novel mechanism of action.
Studies suggest that reducing the activity of IL-6, one of several key
cytokines involved in the inflammatory process, may reduce inflammation of
the joints, prevent long-term damage and relieve certain systemic effects
of RA such as anemia, fatigue and osteoporosis. The ACTEMRA(TM) clinical
development program is designed to evaluate these questions. The compound
is not currently approved in the United States.

About Rheumatoid Arthritis

Rheumatoid arthritis is a progressive, systemic autoimmune disease
characterized by inflammation of the membrane lining in the joints. This
inflammation causes a loss of joint shape and function, resulting in pain,
stiffness and swelling, ultimately leading to irreversible joint
destruction and disability. Characteristics of RA include redness,
swelling, pain, and movement limitation around joints of the hands, feet,
elbows, knees and neck that leads to loss of function. In addition, the
systemic symptoms of RA include fatigue, anemia and osteoporosis and may
contribute to shortening life expectancy by affecting major organ systems.
After 10 years, less than 50% of patients can continue to work or function
normally on a daily basis. RA affects more than 21 million people worldwide
with approximately 2.1 million people affected in the United States.

About Roche

Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S.
pharmaceuticals headquarters of the Roche Group, one of the world's leading
research-oriented healthcare groups with core businesses in pharmaceuticals
and diagnostics. For more than 100 years, the Roche Group has been
committed to developing innovative products and services that address
prevention, diagnosis and treatment of diseases, thus enhancing people's
health and quality of life. An employer of choice, in 2005, Roche was named
one of Fortune magazine's Best Companies to Work For in America, one of the
Top 20 Employers (Science magazine), ranked as the No. 3 Best Company to
Work For in NJ (NJ Biz magazine), the No. 1 Company to Sell For (Selling
Power), and one of AARP's Top Companies for Older Workers. For additional
information about the U.S. pharmaceuticals business, visit our websites: rocheusa or roche.us.

Roche

rocheusa

Revealed: Inflammatory Processes In Arteriosclerosis

2011-06-10T18:30:00.000-07:00

Revolutionary new results concerning substances that play major roles in the inflammatory response have been published in the American scientific journal PNAS in two articles from Karolinska Institutet. Inflammation is important in, for example, cardiovascular disease. The results open the way for the development of new drugs both for prevention and for treatment.

Conditions and diseases that involve inflammation include severe infection, arthritis, asthma and arteriosclerosis. Certain substances, such as cytokines, are formed during the inflammation response and contribute to its various aspects. Professor Jesper Haeggstr?¶m and his group, working in close collaboration with Professor Jan Palmblad's group, show in the first of two articles published in Proceedings of the National Academy of Sciences (2 May 2006) that several of these substances can influence the cells of the blood vessel wall such that they start to express receptors for a leukotriene, LTB4.

This enables the cells to react to LTB4 and to transmit signals that reinforce the inflammation. LTB4 is a powerfully chemotactic and immuno-modulating substance that is important for the motion of white blood cells over the walls of the blood vessel when the tissue becomes damaged and inflamed. It has previously been believed that the cells of the blood vessel wall are silent, unable to react to LTB4.

The demonstration of new factors that control the interplay between the blood vessel cells and the white blood cells that are crucial in the inflammatory process will enable the development of new drugs to be targeted against these factors. New drugs may in the long term become available for use during chronic inflammation such as arthritis, asthma and cardiovascular disease.

The second of the two articles presents the first report of a study that has been carried out in collaboration with arteriosclerosis researchers and surgeons at the Karolinska University Hospital, Solna. The study has investigated all enzymes and receptors that are involved in the formation and signalling of leukotrienes in arteriosclerotic tissue (hardened and calcified arteries). The experimental material has been obtained from the biobank Karolinska Endoarterectomies, in which material from patients who have received surgery for hardened arteries has been collected.

Three enzymes that have increased levels in arteriosclerotic tissue have been identified in the study; the levels of two of these enzymes are particularly highly increased in patients who are experiencing or who have recently experienced symptoms of acute vascular disease with the formation of clots. These three enzymes are vital for the formation of the immuno-modulating substance LTB4, and one of them, leukotriene A4 (LTA4) hydrolase, is particularly important. The focus that has now been placed on these critical enzymes and signal substances may accelerate the development of drugs for both the treatment and the prevention of hardening of the arteries and heart attacks.

The research at Karolinska Institutet into eicosanoids, of which both leukotrienes and prostaglandins are examples, has long been in the international vanguard. Professor Bengt Samuelsson was one of three scientists awarded the Nobel Prize in Physiology or Medicine in 1982 for the discovery of these substances, and has participated in the study on leukotrienes and arteriosclerosis. Professor Jesper Haeggstr?¶m is carrying on the work into eicosanoids and is the leader for a major EU project, EICOSANOX (eicosanox/) that is looking at these central substances and the role they play in several major widespread diseases: cardiovascular disease, arteriosclerosis, dementia and cancer.

References:

"Differential induction of BLT receptor expression on human endothelial cells by lipopolysacharide, cytokines, and leukotriene B4". Qui H, Johansson A-S, Sjostrom M. Wan M, Schroder O, Palmblad J, Haeggstrom JZ. PNAS 103: 6913-18, 2 May 2006.

"Expression of 5-lipoxygenase and leukotriene A4 hydrolase in human arterosclerotic lesions correlates with symptoms of plaque instability". Qui H, Gabrielsen A, Agardh HE, Wan M, Wetterholm A, Wong C-H, Hedin U, Swedenborg J, Hansson GK, Samuelsson B, Paulsson-Berne G, Haeggstrom JZ. PNAS 103:8161-6,12 May 2006.

For more information, please contact:

Professor Jesper Z. Haeggstrom

E-mail: jesper.haeggstromki.se

Contact: Sara Alden

Karolinska Institutet

Frequency Of Foot Disorders Differs Between African Americans And Whites

2011-06-09T18:15:00.000-07:00

Common foot disorders such as flat feet, corns and bunions are more prevalent among African Americans than in whites, a new study by University of North Carolina at Chapel Hill researchers has found.

African Americans in the study age 45 or older were three times more likely than whites of the same age to have corns or flat feet (medical name: pes planus). In people who were not obese, African Americans were twice as likely to have bunions (hallux valgus) and hammer toes than whites, said Yvonne M. Golightly, PT, PhD, lead author of the study, titled "Racial Differences in Foot Disorders: The Johnston County Osteoarthritis Project," and a post-doctoral fellow at UNC's Thurston Arthritis Research Center. There were no significant differences by race for bunions or hammer toes among obese participants.

"That suggests there is a real racial difference there, that it's not something where obesity is also playing a role," she said.

Tailor's bunions (inflammation of the joint at the base of the little toe) and high arches (medical name: pes cavus) were nearly five times more common among whites than African Americans.

Golightly will present these results of the study, based on data collected as part of UNC's long-running Johnston County Osteoarthritis Project, on Tuesday, Nov. 9, at the annual scientific meeting of the American College of Rheumatology/Association of Rheumatology Health Professionals in Atlanta.

In the study, 1,536 participants were clinically evaluated for foot disorders from 2006 to 2010. Golightly and study co-authors identified the most common foot disorders and used statistical analysis to compare each foot problem by race, controlling for age, body mass index (BMI) and gender.

"These foot disorders are very common among people age 45 and older, and can lead to more serious problems such as falls, decreased physical activity and decreased quality of life," Golightly said.

"The next step in our research is to determine the origin of these disorders," she said. "We're interested in looking at the influence of factors such as genetics, shoe wear, multi-joint osteoarthritis, and what type of work a person does."

Co-authors of the study are Marian T. Hannan, DSc, MPH and Alyssa B. Dufour, MA, both from Hebrew Senior Life in Boston, and Joanne M. Jordan, MD, MPH, Chief of the Division of UNC Rheumatology, Allergy and Immunology, director of the UNC Thurston Arthritis Research Center and principal investigator of the Johnston County Osteoarthritis Project.

Source: University of North Carolina at Chapel Hill School of Medicine

Researchers Determine Lifetime Risk Of Adult Rheumatoid Arthritis

2011-06-08T18:00:00.000-07:00

Mayo Clinic researchers have determined the lifetime risk of developing rheumatoid arthritis and six other autoimmune rheumatic diseases for both men and women. The findings appear online in Arthritis and Rheumatism.

"We estimated the lifetime risk for rheumatic disease for both sexes, something that had not been done before -- separately or collectively," says Cynthia Crowson Mayo Clinic biostatistician and first author. "Prevalence and incidence rates existed, but prevalence figures underestimate individual risk and incidence rates express only a yearly estimate."

The researchers were looking for an accurate basis to offer an easy-to-understand average risk over a person's lifetime, knowing that risk changes at almost every age. They used data from the Rochester Epidemiology Project, a long-term epidemiology resource based on patients in Olmsted County, Minn. The cohort of 1179, consisted of patients diagnosed between 1955 and 2007, allowed the team to extrapolate the nationwide estimates.

The adult lifetime risk in the United States of having some kind of inflammatory autoimmune disease is 8.4 percent for women and 5.1 percent for men. Based on year 2000 population figures, that means one woman in 12 and one man in 20 will develop one of the conditions in their lifetime. The authors consider that a substantial risk and say their findings should encourage more research on the value of early diagnosis and intervention for people with increased genetic risk of arthritis. They hope the new figures will help in counseling patients and in fundraising efforts to find improved treatments.

The figures below reflect lifetime risk for the respective diseases, based on the Mayo findings.

Disease Women Men

Rheumatoid Arthritis (RA)

3.6% or 1 in 28 1.7% or 1 in 59

Polymyalgia Rheumatica 2.4% 1.7%

Systemic Lupus Erythematosus .9% .2%

Giant Cell Arteritis 1.0% .5%

Psoriatic Arthritis .5% .6%

Primary Sj?¶grens syndrome .8% .04%

Ankylosing Spondylitis .1% .6%

The research was supported by the National Institutes of Health. Other Mayo authors are Eric Matteson, M.D., M.P.H.; Elena Myasoedova, M.D., Ph.D.; Clement Michet, M.D.; Floranne Ernste, M.D.; Kenneth Warrington, M.D.; John Davis III, M.D.; Gene Hunder, M.D.; Terry Therneau, Ph.D.; and Sherine Gabriel, M.D.

Source: Mayo Clinic

Acupuncture relieves pain and improves function in knee osteoarthritis

2011-06-07T17:45:00.000-07:00

Acupuncture provides pain relief and improves function for people with osteoarthritis of the knee and serves as an
effective complement to standard care. This landmark study was funded by the National Center for Complementary and
Alternative Medicine (NCCAM) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), both
components of the National Institutes of Health. The findings of the study--the longest and largest randomized, controlled
phase III clinical trial of acupuncture ever conducted--were published in the December 21, 2004, issue of the Annals of
Internal Medicine.1

The multi-site study team, including rheumatologists and licensed acupuncturists, enrolled 570 patients, aged 50 or older
with osteoarthritis of the knee. Participants had significant pain in their knee the month before joining the study, but had
never experienced acupuncture, had not had knee surgery in the previous 6 months, and had not used steroid or similar
injections. Participants were randomly assigned to receive one of three treatments: acupuncture, sham acupuncture, or
participation in a control group that followed the Arthritis Foundation's self-help course for managing their condition.
Patients continued to receive standard medical care from their primary physicians, including anti-inflammatory medications,
such as COX-2 selective inhibitors, non-steroidal anti-inflammatory drugs, and opioid pain relievers.

"For the first time, a clinical trial with sufficient rigor, size, and duration has shown that acupuncture reduces the pain
and functional impairment of osteoarthritis of the knee," said Stephen E. Straus, M.D., NCCAM Director. "These results also
indicate that acupuncture can serve as an effective addition to a standard regimen of care and improve quality of life for
knee osteoarthritis sufferers. NCCAM has been building a portfolio of basic and clinical research that is now revealing the
power and promise of applying stringent research methods to ancient practices like acupuncture."

"More than 20 million Americans have osteoarthritis. This disease is one of the most frequent causes of physical disability
among adults," said Stephen I. Katz, M.D., Ph.D., NIAMS Director. "Thus, seeking an effective means of decreasing
osteoarthritis pain and increasing function is of critical importance."

During the course of the study, led by Brian M. Berman, M.D., Director of the Center for Integrative Medicine and Professor
of Family Medicine at the University of Maryland School of Medicine, Baltimore, Maryland, 190 patients received true
acupuncture and 191 patients received sham acupuncture for 24 treatment sessions over 26 weeks. Sham acupuncture is a
procedure designed to prevent patients from being able to detect if needles are actually inserted at treatment points. In
both the sham and true acupuncture procedures, a screen prevented patients from seeing the knee treatment area and learning
which treatment they received. In the education control group, 189 participants attended six, 2-hour group sessions over 12
weeks based on the Arthritis Foundation's Arthritis Self-Help Course--a proven, effective model.

On joining the study, patients' pain and knee function were assessed using standard arthritis research survey instruments and
measurement tools, such as the Western Ontario McMasters Osteoarthritis Index (WOMAC). Patients' progress was assessed at 4,
8, 14, and 26 weeks. By week 8, participants receiving acupuncture were showing a significant increase in function and by
week 14 a significant decrease in pain, compared with the sham and control groups. These results, shown by declining scores
on the WOMAC index, held through week 26. Overall, those who received acupuncture had a 40 percent decrease in pain and a
nearly 40 percent improvement in function compared to baseline assessments.

"This trial, which builds upon our previous NCCAM-funded research, establishes that acupuncture is an effective complement to
conventional arthritis treatment and can be successfully employed as part of a multidisciplinary approach to treating the
symptoms of osteoarthritis," said Dr. Berman.

Acupuncture--the practice of inserting thin needles into specific body points to improve health and well-being--originated in
China more than 2,000 years ago. In 2002, acupuncture was used by an estimated 2.1 million U.S. adults, according to the
Centers for Disease Control and Prevention's 2002 National Health Interview Survey.2 The acupuncture technique that has been
most studied scientifically involves penetrating the skin with thin, solid, metallic needles that are manipulated by the
hands or by electrical stimulation. In recent years, scientific inquiry has begun to shed more light on acupuncture's
possible mechanisms and potential benefits, especially in treating painful conditions such as arthritis.

For credentialed media: B-roll of acupuncture of the knee will be available through NCCAM. NCCAM and NIAMS will hold a
telebriefing to share results on Monday, December 20, 2004 at 10:30 a.m. ET. To request B-roll or learn about the
telebriefing, call NCCAM's press office at 301-496-7790. A video news release (VNR) will also be available from the American
College of Physicians, publishers of Annals of Internal Medicine. For VNR information, please contact Leigh Fazzina at
1-800-523-1546, ext. 2514. Interviews with the principal investigator, Dr. Brian Berman, may be arranged through Sharon
Boston of the University of Maryland School of Medicine public affairs office at 410-328-8919. The Web site for the Center
for Integrative Medicine at the University of Maryland School of Medicine is compmed.umm.

The National Center for Complementary and Alternative Medicine (NCCAM) is dedicated to exploring complementary and
alternative medical (CAM) practices in the context of rigorous science, training CAM researchers, and disseminating
authoritative information to the public and professionals. For additional information, call NCCAM's Clearinghouse toll free
at 1-888-644-6226, or visit the NCCAM Web site at nccam.nih.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is to support research into
the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical
scientists to carry out this research, and the dissemination of information on research progress in these diseases. For
additional information, call NIAMS's Clearinghouse toll free at 1-877-22-NIAMS, or visit the NIAMS Web site at niams.nih.

1. Berman BM, Lao L, Langenberg P, Lee WL, Gilpin AMK, Hochberg MC. Effectiveness of Acupuncture as Adjunctive Therapy in
Osteoarthritis of the Knee: A Randomized, Controlled Trial. Annals of Internal Medicine. 2004; 141(12):901-910.

2. Barnes P, Powell-Griner E, McFann K, Nahin R. CDC Advance Data Report #343. Complementary and Alternative Medicine Use
Among Adults: United States, 2002. May 27, 2004.

Contact: NCCAM Press Office

nccampressmail.nih

301-496-7790

NIH/National Center for Complementary and Alternative Medicine

Disease Markers That Will Aid Arthritis Research

2011-06-06T17:30:00.000-07:00

A combination of biochemical and MRI markers will allow improved measurement of osteoarthritis (OA) progression. The biomarkers, described in BioMed Central's open access journal Arthritis Research and Therapy, will be useful for the design and interpretation of trials of new disease modifying drugs.

Erik Dam, from Nordic Bioscience, Denmark, worked with a team of researchers to develop and evaluate the markers. He said, "Presently, there is no disease-modifying OA drug with a consistent, documented effect despite several clinical attempts in late stage phases. We believe that effective therapies could be demonstrated, if tools were available that allow identification of rapid progressors for inclusion in trials. With this in mind, we investigated whether combinations of biochemical and MRI-based biomarkers might improve diagnosis and prognosis of knee osteoarthritis".

Dam and his colleagues included 159 subjects in their trial. After exclusions, a total of 287 knees were measured. At baseline and after 21 months, biochemical (urinary collagen type II C-telopeptide fragment, CTX-II) and MRI-based markers were quantified. MRI markers included cartilage volume, thickness, area, roughness, homogeneity, and curvature in the medial tibio-femoral compartment. Joint space width, the presently accepted marker for population selection in clinical studies, was measured from radiographs. According to Dam, "The best individual diagnostic marker was cartilage roughness and the best individual prognostic marker was homogeneity. The aggregate cartilage longevity marker (combining CTX-II, volume, area, thickness, congruity, roughness, and homogeneity) performed very well both diagnostically and prognostically - and superior to the individual biochemical and MRI markers. We attribute this to the combination of markers with complementary information about cartilage quantity (e.g. volume), quality (e.g. homogeneity), and breakdown (CTX-II) that together allow superior diagnosis/prognosis".

The proposed aggregate marker methodology may have a direct impact on the design of clinical studies. The researchers claim, "By allowing the selection of a high risk population, the study sample size can be lowered while still improving the chance of a positive study outcome. This should facilitate the development of effective drugs".

Notes:
Identification of progressors in osteoarthritis by combining biochemical and MRI-based markers

Erik B Dam, Marco Loog, Claus Christiansen, Inger Byrjalsen, Jenny Folkesson, Mads Nielsen, Arish A Qazi, Paola C Pettersen, Patrick Garnero and Morten A Karsdal

Arthritis Research & Therapy (in press) arthritis-research/

Source:
Graeme Baldwin

BioMed Central

BioCryst To Present New Data For BCX4208 Monotherapy At The 74th Annual American College Of Rheumatology (ACR) Scientific Meeting

2011-06-05T17:15:00.000-07:00

BioCryst Pharmaceuticals, Inc. (NASDAQ: BCRX) announced the presentation of new data related to the efficacy and safety of BCX4208 for the treatment of gout at the 74th ACR Scientific Meeting being held in Atlanta, Georgia.

The data will be presented during a poster session scheduled for today, November 8, 2010 from 9:00-11:00 a.m. Eastern Time. The poster to be presented during the session is entitled:

-- "Effects of a Purine Nucleoside Phosphorylase Inhibitor, BCX4208, on the Serum Uric Acid Concentrations in Patients with Gout". This poster concludes that BCX4208 doses administered at 40, 80, 120, 160 and 240 mg once-daily monotherapy rapidly and significantly reduced serum uric acid (sUA) in patients with gout. BCX4208 was generally safe and well-tolerated at the doses evaluated in this study.

About BCX4208

BCX4208 is a next generation purine nucleoside phosphorylase (PNP) inhibitor with the potential for once-a-day dosing suitable for chronic administration. With its unique mechanism of action, clinical activity and safety in clinical studies to date as well as its potential synergy with approved therapies, BCX4208 has the potential to address unmet medical needs across a broad spectrum of inflammatory and autoimmune diseases. In September 2010, BioCryst reported positive results from its Phase 2 study of BCX4208 alone and in combination with allopurinol in patients with gout, announcing that the study met its primary endpoint related to serum uric acid (sUA) reduction, demonstrated a dose-response for both BCX4208 and allopurinol, and that the combination of BCX4208 and allopurinol was shown to be superior to either drug alone in sUA reduction.

Forward-Looking Statements

This press release contains forward-looking statements, including statements regarding future results, performance or achievements. These statements involve known and unknown risks, uncertainties and other factors which may cause our actual results, performance or achievements to be materially different from any future results, performances or achievements expressed or implied by the forward-looking statements. These statements reflect our current views with respect to future events and are based on assumptions and subject to risks and uncertainties. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Some of the factors that could affect the forward-looking statements contained herein include: that ongoing and future pre-clinical and clinical development of BCX4208 may not have positive results; that we or our licensees may not be able to enroll the required number of subjects in planned clinical trials of our product candidates and that such clinical trials may not be successfully completed; that BioCryst or its licensees may not commence as expected additional human clinical trials with our product candidates; that our product candidates may not receive required regulatory clearances from the FDA; that ongoing and future pre-clinical and clinical development may not have positive results; that we or our licensees may not be able to continue future development of our current and future development programs; that our development programs may never result in future product, license or royalty payments being received by BioCryst; that BioCryst may not be able to retain its current pharmaceutical and biotechnology partners for further development of its product candidates or it may not reach favorable agreements with potential pharmaceutical and biotechnology partners for further development of its product candidates; that our actual cash burn rate may not be consistent with our expectations; that BioCryst may not have sufficient cash to continue funding the development, manufacturing, marketing or distribution of its products and that additional funding, if necessary, may not be available at all or on terms acceptable to BioCryst. Please refer to the documents BioCryst files periodically with the Securities and Exchange Commission, specifically BioCryst's most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and current reports on Form 8-K, all of which identify important factors that could cause the actual results to differ materially from those contained in our projections and forward-looking statements.

Source: BioCryst

Repurposing Of Enbrel For Alzheimer's Disease

2011-06-04T17:00:00.000-07:00

At Cambridge Healthtech Institute's Third Annual Drug Repositioning Summit on Monday, October 6 in Boston, the audience is scheduled to hear, as a Keynote Presentation, the story of how an individual physician has charted an entirely new course for a therapeutic which is already one of the most successful of all time.

Enbrel® (etanercept) has proven effective for treating a host of medical conditions, from rheumatoid arthritis to psoriasis, generating more than $4 billion dollars per year in revenue for its owner, Amgen. Yet despite this success Amgen has failed to initiate study of etanercept's emerging off-label uses in the field of neurology, which could potentially address enormous unmet medical needs and help people throughout the world. Etanercept is one of a new class of medications, produced through biotechnology, which specifically neutralize an immune signaling molecule called TNF. Excess TNF is centrally involved in scores of diseases, including rheumatoid arthritis, Alzheimer's, sciatica pain, and psoriasis. In Alzheimer's disease excess TNF has been documented in the cerebrospinal fluid, and the rationale for anti-TNF treatment is supported by genetic, epidemiologic, basic science, and clinical data (1-11).

The Keynote Presentation, entitled "Repurposing of Enbrel for Alzheimer's Disease" will be made by Edward Tobinick MD, Director of the Institute for Neurological Research, a private medical group, inc. in Los Angeles. Dr. Tobinick is the inventor and patent holder of the etanercept off-label indication for Alzheimer's Disease, as well as more than 200 different inventions involving new off-label uses of TNF blockers, such as etanercept, in neurology, opthalmology, and for a variety of additional innovative clinical indications(12-17). Many of the novel uses of etanercept which Dr. Tobinick invented, beginning nearly a decade ago, such as for sciatica, Alzheimer's, and myasthenia gravis, have subsequently been supported by peer-reviewed, published studies performed by independent researchers from academic centers across the globe(18-26).

As an example, a recently completed, double-blind, placebo-controlled study conducted by independent researchers at Johns Hopkins/Walter Reed Army Medical Center has confirmed the efficacy of etanercept for sciatica, using a patented, perispinal method of administration of etanercept which Dr. Tobinick invented(27).

Dr. Tobinick has been invited to and has presented his clinical and research findings at multiple prestigious medical research meetings, including this year's International Congress on Alzheimer's Disease (ICAD 2008), the 7th International Alzheimer's Drug Discovery Conference; at the Karolinska Institutet in Stockholm, Sweden, the home of the Nobel Prize in medicine; and in multiple, peer-reviewed, published medical articles(1-5, 27-31).

His published, peer-reviewed scientific articles have been cited by more than 150 scientific publications from around the world(1-6, 18, 20, 23-25, 32, 33). In addition, his groundbreaking work has been recognized by the Dana Alliance for Brain Initiatives, the world's leading organization of neuroscientists, which counts among its members ten Nobel Laureates(34); by leading journals, including Nature Clinical Practice Neurology(35); by the Faculty of 1000 Biology, the expert guide to the most important advances in biology(36); and featured in news articles from around the world(37-39). Despite the immense potential to help countless people, the great unmet medical need, and their enormous continuing revenue from etanercept sales, Amgen has yet to confirm its intention to begin even preliminary clinical study in this direction.

A failure to investigate is perhaps even more puzzling in view of the increasing scientific support from cutting edge research, which is in addition to the genetic studies which have identified excess TNF as a therapeutic target in Alzheimer's(9, 10, 33, 40-43). For example, scientists from the Trinity College Institute of Neuroscience in Ireland have demonstrated that defects in hippocampal learning and memory mechanisms created by forms of amyloid are mediated by TNF(41-43). Perhaps even more significant is the recent identification of TNF as a gliotransmitter which regulates synaptic transmission in the brain(39, 44, 45).

The synaptic effects of TNF which regulate learning, memory, and neurotransmission provide a most exciting area for scientific research. These synaptic effects, which may occur with extreme rapidity, provide a rational and scientifically plausible explanation for the rapid clinical effects of etanercept which have been documented in multiple, peer-reviewed scientific studies and in multiple patients(1-5, 18, 28, 30). To ignore this new direction in scientific thinking, which recognizes the role of TNF not just in inflammation but also as an immune regulator of synaptic communication and other aspects of brain function, would be to impede scientific progress.

Fortunately, with the expiration of Amgen's patents on etanercept approaching in 2012, other pharmaceutical companies will soon have the ability to explore these extraordinary discoveries which have the potential to help millions of patients around the world.

The Keynote Presentation will cover over ten years of research, highlighting the difficult hurdles which new breakthroughs in science and medicine must surmount before they are even considered by the scientific and medical communities.

For further information on this Keynote Presentation, please visit AlzheimerVideoNews , or the INR® website.

Institute for Neurological Research

View drug information on Enbrel.

Hand Osteoarthritis' Aggressive Nature

2011-06-03T16:45:00.000-07:00

In just two years, patients with hand osteoarthritis (OA) experienced a significant increase in pain and functional limitations, according to new data presented at EULAR 2007, the Annual European Congress of Rheumatology in Barcelona, Spain. Statistically significant radiological progression was also detected in 20% of subjects.

OA is the most common form of arthritis. It generally affects older people, especially women and can occur in multiple areas of the hand and wrist, causing pain and stiffness and affecting everyday activities requiring fine motor control and hand grip e.g. writing. Over time, if left untreated, the bones that make up the joint can lose their normal shape, causing further pain and limited motion. However, knowledge about the progression of hand OA and effective therapies to prevent its progression has been lacking.

Led by Dr Stella Botha-Scheepers of Leiden University, The Netherlands, this study followed 172 patients (mean age 60.5 years, 78.5% women) with hand OA (defined by the American College of Rheumatology criteria) for two years, assessing: pain intensity upon lateral pressure in the DIP, IP, PIP and CMC 1 joints on a four-point scale; self-reported hand pain and functional limitations with subscales of the Australian/Canadian Osteoarthritis Hand Index (AUSCAN LK 3.0); and osteophytes and joint space narrowing in the right and left DIP joints, IP joints of the thumbs, PIP joints and CMC 1 joints through standardized radiographs.

Despite a relatively short follow-up period of two years, statistically significant increases in pain intensity on lateral pressure standard response mean (SRM) 0.67), AUSCAN pain scores (SRM 0.25) and AUSCAN function scores (SRM 0.23) occurred. Statistically significant radiological progression was also seen in 20% of patients, in terms of joint space narrowing (SRM 0.34) and osteophytes (SRM 0.35), with progression of osteophytes occurring more often in women and middle-aged patients, and especially in women in an early post-menopausal stage.

Dr Botha-Scheepers commented: "The findings of this study underline the critical need for early, effective intervention in hand OA to prevent irreversible progression, given the dramatic deterioration of clinical and radiological disease status seen in just two years."

Hand OA tends to appear in a predictable pattern, most commonly affecting the small joints of the fingers and the joint at the base of the thumb. It can be diagnosed by medical examination and X-rays of the hand. Treatment options for arthritis of the hand and wrist include oral medication, injections, splinting and surgery.

Abstract number: OPO029

About EULAR

* The European League Against Rheumatism (EULAR) is the organization which represents the patient, health professional and scientific societies of rheumatology of all the European nations.

* The aims of EULAR are to reduce the burden of rheumatic diseases on the individual and society and to improve the treatment, prevention and rehabilitation of musculoskeletal diseases. To this end, EULAR fosters excellence in education and research in the field of rheumatology. It promotes the translation of research advances into daily care and fights for the recognition of the needs of people with musculoskeletal diseases by the governing bodies in Europe.

* Diseases of bones and joints, such as rheumatoid arthritis and osteoarthritis cause disability in 4 - 5 % of the adult population and are predicted to rise as people live longer.

* As new treatments emerge and cellular mechanisms are discovered, the 8th Annual European Congress of Rheumatology in Barcelona (EULAR 2007) brings together more than 10,000 experts - scientists, clinicians, healthcare workers, pharmaceutical companies and patients - to share their knowledge in a global endeavour to challenge the pain and disability caused by musculo-skeletal disorders.

* To find out more information about the activities of EULAR, visit: eular/

Contact: Rory Berrie

European League Against Rheumatism

Enzyme's newly discovered role may make it target for arthritis treatment

2011-06-02T16:30:00.000-07:00

Scientists have found a new role for a previously identified enzyme that may make it a target for anti-inflammatory
treatments.

The finding by researchers at Washington University School of Medicine in St. Louis shows that an enzyme known as cathepsin G
regulates the ability of immune cells known as neutrophils to secrete chemicals that attract other immune cells and start the
local inflammatory process. Over time, the excessive accumulation of immune cells can lead to tissue and cartilage damage in
joints, causing pain and limiting mobility.

"Cathepsin G affects a very early step in this kind of immune response, so inhibiting it has attractive potential for
developers of therapeutics," says senior author Christine T.N. Pham, M.D., assistant professor of medicine and a
rheumatologist at Barnes-Jewish Hospital.

The study appears in the June 2005 issue of Immunity.

Cathepsin G, which is made by the neutrophils it regulates, is also an attractive target because it belongs to a class of
enzymes known as proteases. One principal type of treatment for HIV, the virus that causes AIDS, inhibits proteases, so
scientists who try to block cathepsin G's role in inflammation will already have an extensive body of research results to
refer to.

Pham's lab uses mouse models of arthritis to study the contributions of proteases and other factors to inflammation and
arthritis. One such model involves injecting mice with collagen from calf joints.

"The mice make antibodies to that protein because it's somewhat foreign, but the antibodies have enough cross-reactivity that
they will bind to the mouse's own cartilage and collagen and initiate an inflammation," Pham explains. "This leads to a
condition similar to rheumatoid arthritis in the mice."

Three years ago, Pham's lab published results showing that mice deficient in cathepsin G and other closely related proteases
failed to develop arthritis after the injections. This led them to look for the mechanisms by which these proteases regulate
inflammation.

Observations made by Pham's lab and other groups had linked the earliest stages of inflammation in the animal models to
neutrophils, which are a kind of immune system firestarter. They arrive first at sites of injury, infection or irritation and
secrete chemicals that bring in secondary waves of other immune attack cells.

"The contributions of the neutrophil weren't always appreciated by scientists," Pham notes. "When patients come to their
doctors with arthritis symptoms, the inflammation typically is so well-established that neutrophils are no longer the
predominant cell type."

Animal models of inflammation let scientists watch all stages of the inflammatory process and allowed them to see how
important neutrophils are to the early stages of that process.

In the new study, Pham and her colleagues showed that cathepsin G is secreted by neutrophils, binds to the cells' surface
membranes, and affects the rearrangement of integrins, an important group of adhesion compounds on the surface of
neutrophils.

"The way these integrins rearrange and cluster on the cell surface can send a signal back into the cell that modifies the
cell's behavior, allowing it to do things like secrete inflammatory factors," Pham explains. "The proteases' ability to
affect integrin rearrangement is dependent on their catalytic activity, and that's an ability that can be taken away from
them."

Pham suspects this class of proteases may also be making significant contributions to other autoimmune and inflammatory
conditions besides arthritis. She plans further studies to investigate this possibility. Her lab is also working to determine
what molecules cathepsin G is sticking to and interacting with on the surfaces of neutrophils and other cells.

Raptis SZ, Shapiro SD, Simmons PM, Cheng AM, Pham CTN. Serine protease Cathepsin G regulates adhesion-dependent neutrophil
effector functions by modulation integrin clustering. Immunity, June 7, 2005, 679-691.

Funding from the Arthritis Foundation and the National Institutes of Health supported this research.

Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of
Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and
patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its
affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Contact: Michael C. Purdy

purdymwustl

314-286-0122

Washington University School of Medicine

medinfo.wustl

Congressional Hearing Focuses on Merck's Marketing for COX-2 Drug Vioxx

2011-06-01T16:15:00.000-07:00

Merck sales associates were given detailed instructions not to mention certain potential cardiovascular risks when promoting the company's COX-2 inhibitor Vioxx to doctors, according to an analysis of 20,000 pages of internal documents by congressional investigators for the... House Committee on Government Reform delivered at a hearing Thursday, the Washington Post reports (Kaufman, Washington Post, 5/6). Merck in September 2004 voluntarily withdrew Vioxx from the market, citing cardiovascular safety risks.

Vioxx Marketing History
In March 2000, a Merck-funded study called VIGOR showed increased heart attack risks associated with Vioxx (Cohen, Newark Star-Ledger, 5/6). The study showed a fivefold increase in heart attacks among those who took Vioxx compared with those who took the painkiller naproxen. Merck said that the findings possibly were a result of a protective effect on the heart that naproxen provided, not an increased risk associated with Vioxx (Appleby, USA Today, 5/6). According to company documents included in the congressional investigation, Merck in April 2000 developed a "Cardiovascular Card" for use in sales representatives' presentations to physicians. According to the committee, Merck's 3,000 sales representatives were instructed to refer doctors who raised questions about cardiovascular risks to the card, which indicated that Vioxx was eight to 11 times safer than other similar painkillers. Information on the card was taken from several studies submitted to FDA and omitted any reference to the VIGOR study. An FDA advisory committee in 2001 voted that physicians should be informed of the VIGOR study findings. According to the committee, Merck subsequently sent a memo to sales representative that stated, "Do not initiate discussions of the FDA arthritis committee ... or the results of the ... VIGOR study." Further, representatives were specifically directed to respond to doctors' questions about the study by saying, "I cannot discuss the study with you" (Newark Star-Ledger, 5/6). Additional cardiovascular risks of Vioxx were cited in an August 2001 study in the Journal of the American Medical Association (USA Today, 5/6).

Label Change, Sales Instructions
After "extensive negotiations" with FDA, Merck in April 2002 agreed to a label change for Vioxx that included risks found in the VIGOR study. The label also included a statement that the significance of the findings was "unknown." According to the committee, Merck told sales representatives "to emphasize the uncertainty of the VIGOR study to counter physicians' concerns," the Star-Ledger reports (Newark Star-Ledger, 5/6). Sales representatives were told to encourage doctors to submit any questions in writing to Merck's medical services department. The company received 123,000 inquiries from physicians, according to Dennis Erb, Merck's vice president for regulatory issues (Alonso-Zaldivar, Los Angeles Times, 5/6).

Sales Techniques
According to the Post, Merck documents unearthed in the investigation indicate that sales representatives were given detailed instructions about how to approach physicians when selling Vioxx. "They were trained how to smile, speak and position themselves most effectively when talking with doctors," the Post reports (Washington Post, 5/6). Representatives also were instructed how to use "verbal and nonverbal" cues to gain a physician's trust. Training materials indicated that representatives should shake a doctor's hand for no longer than three seconds. Merck officials also informed representatives about "different personality types of doctors and recommended [sales] techniques for each type," the Star-Ledger reports (Newark Star-Ledger, 5/6). The training included motivational courses in which representatives were "taught not to take no for an answer." The courses compared milestones in sales of Merck drugs to points in the lives of Martin Luther King and Helen Keller. Campaigns were titled "Project Offense" and "Project XXcelleration." In documents, doctors' concerns about risks were termed "obstacles." The company also used "sophisticated databases" to track the prescribing patterns of individual doctors and set targets for sales, according to the Los Angeles Times (Los Angeles Times, 5/6). Representatives were given $2,000 bonuses for meeting sales goals (AP/New York Times, 5/6). According to the Los Angeles Times, Merck's marketing campaign was "astoundingly successful," with the "overwhelming majority" of prescriptions dispensed after concerns about heart risks had surfaced. Vioxx achieved sales of $2 billion annually "faster than any previous Merck drug," the Los Angeles Times reports (Los Angeles Times, 5/6).

Committee Report
The committee report states, "When concerns about Vioxx's safety arose, Merck appeared to use this highly trained force to present a misleading picture to physicians about the drug's cardiovascular risks." The report also said that Merck instructed its sales force to "emphasize outdated and misleading data that indicated Vioxx was safer than alternatives" (Newark Star-Ledger, 5/6). Committee ranking member Henry Waxman (D-Calif.) at the hearing said, "This sales force is given extraordinary training so that it can capitalize on virtually every interaction with doctors. Yet when it comes to the one thing doctors most need to know about Vioxx -- its health risks -- Merck's answer seems to be disinformation and censorship" (Washington Post, 5/6). He asked, "Why did doctors write so many Vioxx prescriptions even as evidence of harm mounted?" He added that the company's "goal was sales, not education" (AP/New York Times, 5/6). Rep. Gil Gutknecht (R-Minn.) called Merck's omission of potential risks in its presentations "confusing and, in some respects, embarrassing." He added that no one "wants to take responsibility for putting out information that an outside observer might call ... disingenuous."

FDA Testimony
FDA officials at the hearing testified that they were unaware of the details of Merck's marketing campaign, the Los Angeles Times reports (Los Angeles Times, 5/6). Steven Galson, director of FDA's Center for Drug Evaluation and Research, said that Merck is legally obligated only to provide information that was approved in drug labeling (Newark Star-Ledger, 5/6). Galson said that that the promotional materials used by Merck sales representatives were "accurate based on the label, which was the standard we use" (Rovner, Congress Daily, 5/5). However, Galson added that is "important that the company convey truthful information that is up to date." He also said that Merck appears not to have given doctors "the entire picture" (Newark Star-Ledger, 5/6). Galson acknowledged that the agency may have taken too long to remove Vioxx from the market (CQ HealthBeat, 5/6). However, he said FDA is taking steps to improve awareness of drug risks (New York Times, 5/6). "The most important lesson ... is that the American public, practitioners and patients want to get clear and accurate information ... in their own health care decisions," Galson said. Addressing Galson, Gutknecht said, "It seems to me there's a disconnect here. You're saying your policies are legal, but are they ethical? Isn't this the scandal?" (Washington Post, 5/6). Gutknecht also said, "Both the FDA and the pharmaceutical company sort of missed the mark" (Tansey, San Francisco Chronicle, 5/6).

Merck Response
Erb said at the hearing, "We believe Merck acted appropriately and responsibly to extensively study Vioxx after it was approved for marketing to gain more clinical information about the medicine." He added that the company "promptly disclosed the results of those studies to the FDA, physicians, the scientific community and the media" (Los Angeles Times, 5/6). When asked by Committee Chair Tom Davis (R-Va.) whether a "wide awake" physician would have been aware of the drug's risks, Erb said, "That is correct" (AP/New York Times, 5/6). Erb added, "We believed wholeheartedly in the safety of Vioxx and that Vioxx was an important treatment option. My own father was a regular user of Vioxx" (Freking, AP/Las Vegas Sun, 5/6).

Implications
According to the San Francisco Chronicle, the committee's findings "could bolster moves by Congress to beef up the FDA's powers" (San Francisco Chronicle, 5/6). Davis said, "As the committee conducted its investigation, it became apparent that the relationship between the Office of New Drugs and the Office of Drug Safety has its challenges." He said that the challenges include "a lack of communication between the offices, as well as communication up the chain of command" (CongressDaily, 5/5). The committee report could also "prove a bonanza to plaintiffs in civil suits" against Merck alleging that Vioxx caused severe side effects or death, the Chronicle reports (San Francisco Chronicle, 5/6).

Vioxx Return?
Erb said that Merck is in "preliminary discussions," with FDA to determine whether to apply for approval to resume marketing Vioxx in the United States. An FDA advisory committee in February "narrowly" voted to recommend that Vioxx could be allowed back into the U.S. market under certain conditions, the AP/Times reports (AP/New York Times, 5/6).

Gilmartin Resigns
In related news, Merck board members on Thursday named Richard Clark as new CEO after former company CEO and Chair Raymond Gilmartin resigned 10 months before his scheduled retirement, the Wall Street Journal reports. However, in an "unusual agreement," the chair position will remain open for one to two years and a three-member executive committee will advise Clark, according to the Journal (Martinez/Lublin, Wall Street Journal, 5/6). Clark, who joined Merck in 1972 as a quality control inspector, has held positions in production, new product planning and strategic planning (Johnson/Agovino, AP/Atlanta Journal Constitution, 5/6). In 1997, Clark became chief operating officer of the pharmacy benefit manager Medco Health Solutions, which Merck spun off in 2003. Clark became CEO and chair of Medco in 2002 and returned to Merck in 2003 after the spin off. Lawrence Bossidy, a former CEO of Honeywell International, will lead the executive committee and likely will become a "key player in deciding strategy" for Merck. The other executive committee members will include former Princeton University President William Bowen, who will advise Clark on litigation and corporate governance, and Harvard University professor of medicine Samuel Thier, who will advise Clark on health care policy (Wall Street Journal, 5/6). Bossidy also will serve as acting Merck chair at board meetings. Gilmartin, who will remain with Merck as a special adviser to the executive committee until 2006, said that he decided to resign voluntarily (Berenson, New York Times, 5/6). Bossidy said that the executive committee will "work closely" with Clark for as long as two years and "provide support and continuity" (Bloomberg/Los Angeles Times, 5/6). Clark said, "I can guarantee you that I would not take this job if I didn't have full responsibility as the CEO of the company" (McCoy/Appleby, USA Today, 5/6). According to the Journal, Merck board members had some concerns about whether to name an internal candidate as the new CEO but concluded that external candidates were not "head and shoulders above someone who demonstrated repeatedly that he can get results" (Wall Street Journal, 5/6).

"Reprinted with permission from kaisernetwork kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

View drug information on Vioxx.

Red meat consumption rheumatoid arthritis link

2011-05-31T16:00:00.000-07:00

Study indicates high levels of red meat consumption as an independent risk factor in the development of inflammatory
arthritis,

A chronic inflammatory disease of the immune system, rheumatoid arthritis (RA) has been linked to a combination of genetic
and environmental factors. Aspects of lifestyle may explain as much as 40 percent of the risk.

Cigarette smoking has
consistently been found to play a role in RA's development. The role of nutritional factors is less certain. Studies have
suggested the protective benefits of eating fish, the dangers of drinking coffee, and a reduction in disease risk for women
who enjoy alcohol in moderation. Such associations, however, are still wide open to debate and further research.

Recently, a team of British researchers found that a diet lacking in fruit, especially varieties high in vitamin C, increases
the risk of inflammatory arthritis, a common early sign of RA, as much as three-fold. Building on this compelling finding,
they set out to investigate the association of other dietary habits with the onset of RA. Their results, published in the
December 2004 issue of Arthritis & Rheumatism (interscience.wiley/journal/arthritis), indicate a high level of red meat consumption as an
independent risk factor for inflammatory arthritis.

Led by Professors Alan Silman and Deborah Symmons at the University of Manchester, the team drew its subjects from a large,
established research sample--over 25,000 men and women between the ages of 45 and 75 enrolled in the European Prospective
Investigation of Cancer in Norfolk, England. Within this population, 88 new patients with inflammatory arthritis, affecting
at least two major joints, were identified.

Nearly 40 percent of these patients satisfied the American College of Rheumatology criteria for RA at baseline. The patients
were then matched, for age, sex, and body mass index, with 176 controls. At the study's onset, each participant completed a
detailed 7-day food diary, with advance instruction on measuring food portions to help them be as specific as possible in
recording their intake. Each participant also supplied information on his or her past and present status as a smoker.

Patients were more likely to have been former smokers; only 35 percent of the patients had never smoked compared with 85
percent of the controls. In terms of dietary factors, patients and controls were similar in most areas, including intake of
total calories, fat grams, and vitamin D, as well as coffee, tea, and alcohol consumption. Patients had a lower intake of
vitamin C, although the association of this factor with disease risk was not as strong as it was in the team's previous
study. The most striking difference between the two groups was directly related to red meat consumption. After adjusting for
smoking and other possible dietary confounders, patients with the highest level of red meat consumption had a two-fold risk
for the development of RA. Patients who consumed high levels of red meat combined with other meat products showed similar
high risk levels. Interestingly, a higher level of protein intake from all dietary sources was also associated with an
increased disease risk, while higher levels of dietary fats, including saturated fat, did not have an impact.

Routinely eating burgers and steak, however, may only influence people with a predisposition for RA. "It may be that the high
collagen content of meat leads to collagen sensitization and consequent production of anticollagen antibodies, most likely in
a subgroup of susceptible individuals," the authors note. "Meat consumption may be linked to either additives or even
infectious agents, but, again, there is no evidence as to what might be important in relation to RA."

"A high level of red meat consumption may represent a novel risk factor for inflammatory arthritis or may act as a marker for
a group of persons with an increased risk from other lifestyle causes," Dr. Pattison and colleagues conclude. "It is unclear
whether the association is a causative one."

Article: "Dietary Risk Factors for the Development of Inflammatory Polyarthritis: Evidence for a Role of High Level of Red
Meat Consumption," Dorothy J. Pattison, Deborah P.M. Symmons, Mark Lunt, Ailsa Welch, Robert Luben, Sheila A. Bingham,
Kay-Tee Khaw, Nicholas E. Day, and Alan J. Silman, Arthritis & Rheumatism, December 2004; 50:12; pp. 3804-3812.

John Wiley & Sons, Inc

Lexicon Initiates Phase 2 Clinical Trial Of LX2931 In Patients With Rheumatoid Arthritis

2011-05-30T15:45:00.000-07:00

Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), a biopharmaceutical company focused on discovering and developing breakthrough treatments for human disease, announced that it has initiated a Phase 2 clinical trial of LX2931 in patients with rheumatoid arthritis. LX2931 is an orally-delivered, small molecule drug candidate that has recently completed Phase 1 testing in normal volunteers. Lexicon also successfully completed a drug-drug interaction (DDI) study of LX2931 with methotrexate in patients with rheumatoid arthritis, with no clinically significant drug-drug interactions observed.

"We believe that, as an oral therapy, LX2931 could have advantages over current biologic therapies in treating patients with rheumatoid arthritis," said Philip M. Brown, M.D., J.D., senior vice president of clinical development at Lexicon. "LX2931 has demonstrated potent anti-inflammatory activity in preclinical models of arthritis and inflammation and, importantly, has been well tolerated in combination with methotrexate, the current standard of care first-line therapy."

LX2931 inhibits sphingosine-1-phosphate (S1P) lyase, an enzyme identified by Lexicon scientists as a promising new target on a pathway associated with regulation of the human immune system. Lexicon has previously shown that genetically "knocking out" or "knocking down" S1P lyase in mice substantially decreased the inflammatory response in multiple models of arthritis, inflammation and transplantation.

The Phase 2 clinical trial is designed as a 12-week, randomized, double-blind, placebo-controlled study to evaluate the safety and tolerability of LX2931 and its effects on symptoms associated with rheumatoid arthritis. The study will include multiple centers in the United States and Eastern Europe. The company expects to enroll up to 120 patients with rheumatoid arthritis on stable methotrexate therapy. Three dose levels will be evaluated: a 70 mg dose, a 110 mg dose and a 150 mg dose, each administered once daily. The primary endpoint will be the ACR20, which is defined by the American College of Rheumatology (ACR) as a 20 percent improvement in symptoms associated with rheumatoid arthritis. Multiple secondary endpoints will also be evaluated, including ACR50, ACR70 and DAS28.

In addition to LX2931, Lexicon has two other drug candidates progressing in Phase 2 clinical trials, LX1031 for irritable bowel syndrome and LX1032 for carcinoid syndrome. Furthermore, LX4211 for diabetes has recently completed dosing in a Phase 1 clinical trial.

About Rheumatoid Arthritis

Lymphocytes are a type of white blood cell that play an important role in the immune system. Inappropriate activation of lymphocytes is often associated with autoimmune diseases, a spectrum of disorders in which the immune system malfunctions and causes the body to attack its own organs, tissues and cells. Rheumatoid arthritis is an autoimmune disorder characterized by stiffness, pain, swelling, and limitation of motion in multiple joints. More than 2 million Americans suffer from rheumatoid arthritis, which, if left untreated, can result in disfigurement and disability from irreversible joint damage. According to the National Institutes of Health, autoimmune disorders affect between 14.7 and 23.5 million people in the United States.

About Lexicon

Lexicon is a biopharmaceutical company focused on discovering and developing breakthrough treatments for human disease. Lexicon currently has five drug candidates in development for autoimmune disease, carcinoid syndrome, diabetes, glaucoma and irritable bowel syndrome, all of which were discovered by the company's research team. The company has used its proprietary gene knockout technology to identify more than 100 promising drug targets. Lexicon has focused drug discovery efforts on these biologically-validated targets to create its extensive pipeline of clinical and preclinical programs.

Safe Harbor Statement

This press release contains "forward-looking statements," including statements relating to Lexicon's clinical development of LX2931 and the potential therapeutic and commercial potential of LX2931. This press release also contains forward-looking statements relating to Lexicon's growth and future operating results, discovery and development of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. All forward-looking statements are based on management's current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including those relating to Lexicon's ability to successfully conduct clinical development of LX2931 and preclinical and clinical development of its other potential drug candidates, advance additional candidates into preclinical and clinical development, obtain necessary regulatory approvals, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its drug candidates, that may cause Lexicon's actual results to be materially different from any future results expressed or implied by such forward-looking statements. Information identifying such important factors is contained under "Factors Affecting Forward-Looking Statements" and "Risk Factors" in Lexicon's annual report on Form 10-K for the year ended December 31, 2008, as filed with the Securities and Exchange Commission. Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.

Source: Lexicon Pharmaceuticals, Inc.

UCB's Cimzia(R) Approved In The U.S. For Adult Patients Suffering From Moderate To Severe Rheumatoid Arthritis

2011-05-29T15:30:00.000-07:00

Enzon Pharmaceuticals, Inc. (Nasdaq: ENZN) today announced that the U.S. Food and Drug Administration (FDA) has approved Cimzia®, for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA). Cimzia® (certolizumab pegol), is a PEGylated anti-TNFa (Tumor Necrosis Factor alpha). The product is currently being developed by UCB. Cimzia is one of several products which utilize Enzon's PEGylation technology, including PEG-INTRON®, Macugen®, and Pegasys®.

"Our PEGylation technology continues to enable very important therapeutics like Cimzia, benefiting patients with a wide variety of diseases," said Jeffrey H. Buchalter, Enzon's chairman and chief executive officer.

About CIMZIA®

Cimzia® is the only PEGylated anti-TNF (Tumor Necrosis Factor). Cimzia® has a high affinity for human TNF-alpha, selectively neutralizing the pathophysiological effects of TNF-alpha. Over the past decade, TNF-alpha has emerged as a major target of basic research and clinical investigation. This cytokine plays a key role in mediating pathological inflammation, and excess TNF-alpha production has been directly implicated in a wide variety of diseases. The U.S. Food and Drug Administration (FDA) has approved Cimzia® for reducing signs and symptoms of Crohn's disease and maintaining clinical response in adult patients with moderate to severe active disease who have had an inadequate response to conventional therapy and for the treatment of adults with moderate to severely active rheumatoid arthritis. Cimzia® was approved in Switzerland for induction of a clinical response and for the maintenance of a clinical response and remission in patients with active Crohn's disease who have not responded adequately to conventional treatment in September 2007. UCB is also developing Cimzia® in other autoimmune disease indications. Cimzia® is a registered trademark of UCB PHARMA S.A.

Source
Enzon Pharmaceuticals, Inc.

View drug information on Cimzia; Macugen; Peg-Intron.

Frequency Of Foot Disorders Differs Between African Americans And Whites

2011-05-28T15:15:00.000-07:00

Common foot disorders such as flat feet, corns and bunions are more prevalent among African Americans than in whites, a new study by University of North Carolina at Chapel Hill researchers has found.

African Americans in the study age 45 or older were three times more likely than whites of the same age to have corns or flat feet (medical name: pes planus). In people who were not obese, African Americans were twice as likely to have bunions (hallux valgus) and hammer toes than whites, said Yvonne M. Golightly, PT, PhD, lead author of the study, titled "Racial Differences in Foot Disorders: The Johnston County Osteoarthritis Project," and a post-doctoral fellow at UNC's Thurston Arthritis Research Center. There were no significant differences by race for bunions or hammer toes among obese participants.

"That suggests there is a real racial difference there, that it's not something where obesity is also playing a role," she said.

Tailor's bunions (inflammation of the joint at the base of the little toe) and high arches (medical name: pes cavus) were nearly five times more common among whites than African Americans.

Golightly presented these results of the study, based on data collected as part of UNC's long-running Johnston County Osteoarthritis Project, on Tuesday, Nov. 9, at the annual scientific meeting of the American College of Rheumatology/Association of Rheumatology Health Professionals in Atlanta.

In the study, 1,536 participants were clinically evaluated for foot disorders from 2006 to 2010. Golightly and study co-authors identified the most common foot disorders and used statistical analysis to compare each foot problem by race, controlling for age, body mass index (BMI) and gender.

"These foot disorders are very common among people age 45 and older, and can lead to more serious problems such as falls, decreased physical activity and decreased quality of life," Golightly said.

"The next step in our research is to determine the origin of these disorders," she said. "We're interested in looking at the influence of factors such as genetics, shoe wear, multi-joint osteoarthritis, and what type of work a person does."

Co-authors of the study are Marian T. Hannan, DSc, MPH and Alyssa B. Dufour, MA, both from Hebrew Senior Life in Boston, and Joanne M. Jordan, MD, MPH, Chief of the Division of UNC Rheumatology, Allergy and Immunology, director of the UNC Thurston Arthritis Research Center and principal investigator of the Johnston County Osteoarthritis Project.

Source:

Tom Hughes

University of North Carolina School of Medicine

Number Of Excess Cases Of Coronary Heart Disease Caused By Vioxx, Study

2011-05-27T15:00:00.000-07:00

The arthritis drug Vioxx could have caused an estimated 88 000 - 140 000 excess cases of serious coronary heart disease
in the USA since its launch in 1999, concludes a study published online by The Lancet.

Vioxx (rofecoxib) belongs to a class of cyclo-oxygenase 2 (COX-2) inhibitor selective nonsteroidal anti-inflammatory drugs
(NSAIDs), which are prescribed for the treatment of arthritis. Vioxx was withdrawn from the pharmaceutical market at the end
of September 2004 after use of the drug was linked to heart problems.

David J Graham (Office of Drug Safety, US Food and Drug Administration) and colleagues assessed whether coronary heart
disease risk was increased with either high or standard doses of Vioxx compared with other (NSAIDs) or the COX-2 inhibitor
celecoxib (Celebrex), a drug commonly used as an alternative to Vioxx.

They analysed data from 1???4 million people in California who had used NSAIDs from the beginning of 1999 to September 2004.
Patients had received various NSAIDs, including celecoxib (around 40 000 users), ibuprofen (just under a million users),
naproxen (around 435 000 users), and rofecoxib (around 27 000 users). The investigators found that 8143 individuals had
serious coronary heart disease, 1508 of which had sudden cardiac death. Each case was matched by age and sex to four controls
to enable a comparison of coronary heart disease risk among people taking Vioxx and users of other NSAIDs.

People taking Vioxx had a 34% higher chance of coronary heart disease when compared with people who used other NSAIDs.
Coronary heart disease was 1???6 times more likely among people currently taking standard-dose Vioxx compared with those
currently taking celecoxib and 3???6 times more likely among high-dose users. The study also found that people taking naproxen
had a 14% increased risk of coronary heart disease compared with other NSAIDs. Previous studies have suggested that naproxen
protects against coronary heart disease.

Dr Graham comments: "An estimated 88 000-140 000 excess cases of serious coronary heart disease probably occurred in the USA
over the market life of rofecoxib. The US national estimate of the case-fatality rate (fatal acute myocardial infarction plus
sudden cardiac death) was 44%, which suggests that many of the excess cases attributable to rofecoxib use were fatal.

"In the future, when trials show that a new treatment confers a greater risk of a serious adverse effect than a standard
treatment, we must be much more careful about allowing its unrestrained use."

In an accompanying commentary Simon RJ Maxwell and David J Webb (University of Edinburgh, UK) write that after the withdrawal
of Vioxx increased attention will now focus on the cardiovascular safety of other COX-2 inhibitors (coxibs).

Professor Webb concludes: "It now falls to the manufacturers, under the careful review of the regulatory authorities, to
provide all the evidence that this class of drugs is safe, if necessary including studies that directly address
cardiovascular morbidity as a primary outcome.

Indeed, the experience with coxibs underlines the need for full publication of all clinical trial data generated in support
of newly licensed drugs."

Dr David J Graham, Office of Drug Safety, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville,
MD, USA.T) 301 827 3238

Comment Professor David J Webb, Clinical Pharmacology Unit & Research Unit, Department of Medical Sciences, University of
Edinburgh, Western General Hospital, EDINBURGH, EH4 2XU, UK. T) 0131 537 2006

thelancet

View drug information on Vioxx.

Enrollment begins for osteoarthritis initiative

2011-05-26T14:45:00.000-07:00

Recruitment has begun for the Osteoarthritis Initiative (OAI), a public-private partnership between the National Institutes of Health and industry that funds a multisite contract to create a resource to hasten discovery of biological markers for osteoarthritis (OA).

Men and women age 45 and older at risk for developing OA and those with early disease are eligible to participate. After an initial screening, four centers around the United States plan to each enroll and follow 1,250 adults for five years (total enrollment of 5,000).

Biological specimens (blood, urine, DNA), images (X-rays and magnetic resonance scans) and clinical data will be collected annually.

Biological markers - physical signs or biological substances that indicate changes in bone or cartilage - are critical in diagnosing and monitoring OA and developing new treatments.

Ultimately, results from the OAI may enable doctors to use biological markers to help identify people at risk for OA and people with OA at risk for disease progression. The markers could also help doctors assess the effectiveness of treatments.

The four clinical centers, selected in the summer of 2002, include the University of Maryland School of Medicine/Johns Hopkins University, the Ohio State University Medical Center, the University of Pittsburgh and the Memorial Hospital of Rhode Island/Brown University.

A data coordinating center at the University of California, San Francisco oversees the study conduct and will manage the resulting data. The Ohio State University and University of Pittsburgh centers enrolled their first participants the week of February 23, and centers in Maryland and Rhode Island will begin enrollment in late March and early April.

The clinical centers may be contacted at:

Ms. Raushanah Kareem

University of Maryland

10 South Pine Street, Room 8-34, MSTF

Baltimore, MD 21201

(410) 706-5791 or (866) 565-KNEE (toll free)

Osteoarthritis Initiative

The Ohio State University

198 McCampbell Hall

1581 Dodd Drive

Columbus, OH 43210

(614) 688-3563 or (800) 251-1175 (toll free)

Study Office/GSPH

University of Pittsburgh

4200 Fifth Avenue

Pittsburgh, PA 15213-9910

(800) 872-3653 (toll free)

Osteoarthritis Initiative

Memorial Hospital of Rhode Island/Brown University

ATTN: Doris Moore

111 Brewster Street, CPCP Building, 2nd Floor

Pawtucket, RI 02860

(800) 877-3347 (toll free)

Osteoarthritis, a degenerative condition whose hallmarks are joint pain and limited movement resulting from progressive loss of cartilage, is the most common type of arthritis, especially among older people. It can occur in any joint, but most often affects the hands, knees, hips or spine. There are currently no treatments, other than surgical joint replacement, that significantly change the course of this joint disease, and clinical trials for new therapies are long, difficult and expensive.

The OAI is a federal contract funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institute on Aging (NIA), Office of Research on Women's Health, National Institute of Dental and Craniofacial Research, National Center on Minority Health and Health Disparities and National Center for Complementary and Alternative Medicine, all part of the Department of Health and Human Services' National Institutes of Health. Private funding partners include Merck Research Laboratories; Novartis Pharmaceuticals Corporation; and Pfizer Inc. Private sector funding for the OAI is being managed by the Foundation for the National Institutes of Health.

For information on the OAI, visit The OAI: A Knee Health Study at oai.ucsf/clinics.asp. For general questions, visit niams.nih/ne/press/2001/07_17qa.htm. The NIAMS Office of Communications and Public Liaison (301-496-8190) or the NIA Communications Office (301-496-1752) can also be contacted for information.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at niams.nih.

CONTACT:

Liz Freedman

301-496-8190

Smoking And Rheumatoid Arthritis - Evidence Of Harm Accumulates

2011-05-25T14:30:00.000-07:00

The role of smoking as a risk factor for rheumatoid arthritis was supported by several studies reported at the ACR.

Japanese researchers who undertook a meta-analysis of sixteen studies concluded that the strongest association between smoking history and RA occurred for Rheumatoid Factor positive men (odds ratio 2.85) (Abstract# 749).

Swedish researchers found that current smokers had a higher risk of severe extra-articular manifestations of RA than non-smokers (odds ratio 2.67).

They speculate that smoking may have an impact on disease mechanisms in RA, including those leading to extra-articular disease.

American College of Rheumatology Annual Congress (ACR)

mabthera-ra

New Data Shows ACTEMRA Inhibits Progression Of Joint Destruction And Improves Physical Function Of Patients With Rheumatoid Arthritis

2011-05-24T14:15:00.000-07:00

Roche announced that the innovative new therapy ACTEMRA (tocilizumab) can significantly inhibit structural damage to joints in patients with rheumatoid arthritis (RA) this is a critical measure of effectiveness of an RA treatment. ACTEMRA was also found to improve the patients' physical function after one year of therapy and to significantly increase the disease remission rate.

The results from the LITHE1 trial, being presented at the American College of Rheumatology (ACR) Annual Scientific Meeting in San Francisco, showed that:

-- A greater proportion of patients treated with ACTEMRA in combination with a commonly used RA drug called methotrexate (MTX) benefited from a significant inhibition of structural damage during 12 months of therapy compared to patients treated with MTX alone. The outcome was determined by x-ray evidence of the progression of bone erosions and narrowing of joint spaces. This benefit is important to patients as damage to the joints caused by the disease leads to the disability and pain associated with RA.

-- ACTEMRA improved the patients' ability to perform normal daily activities, as assessed by the Health Assessment Questionnaire (HAQ)2, leading to a better quality of life.

-- Significantly more patients treated with ACTEMRA achieved remission* than those treated with MTX alone (47% vs. 8%). The improvement in remission at one year reinforces the strong remission data seen at 6 months in four additional ACTEMRA phase III trials across multiple RA patient populations.

"The outcome of this study is good news for RA patients as presently many either fail to achieve an adequate response or cannot tolerate therapies currently available," said William M. Burns, Head of the Roche Pharma Division. "New treatment options are needed, particularly those that can target different pathways to bring relief and inhibit joint damage in patients suffering from RA."

"The LITHE study demonstrated that treatment with ACTEMRA inhibited structural joint damage, which is a major cause of disability and loss of physical function for RA patients," said

Joel Kremer, M.D., investigator in the LITHE study and Director of Research at The Center for Rheumatology in Albany, New York. "It is critical to stop joint damage as quickly as possible to avoid joint deformity and to help patients maintain their quality of life."

In the LITHE study, ACTEMRA was generally well tolerated and the overall safety profile after 12 months of treatment was consistent with previously reported 6 month trial data.

ACTEMRA is the first of a new class of drug with a novel mechanism of action that brings new hope to RA patients. It is a humanized interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody which works by suppressing the activity of IL-6, an important trigger of the inflammatory process. This novel mode of action reduces inflammation of the joints and relieves the systemic effects of RA.

Rheumatoid Arthritis - A High Unmet Medical Need

Rheumatoid arthritis is thought to affect over 21 million people worldwide. It is a progressive autoimmune disease characterized by inflammation of the membrane lining in the joints throughout the body. This inflammation causes distortion of the joint and impaired function accompanied by pain, stiffness and swelling and ultimately leading to irreversible joint destruction and disability. In addition, the systemic symptoms of RA include fatigue, anaemia, osteoporosis and may contribute to shortening life expectancy by affecting major organ systems. After 10 years, less than 50% of patients can continue to work or function normally on a daily basis.

About the LITHE study

The LITHE study, a randomized, double-blind, placebo-controlled trial was designed to evaluate the efficacy of TCZ plus MTX in preventing structural joint damage and improving physical function. LITHE is an international study, including 15 countries and 1196 patients with moderate to severe RA who had an inadequate response to MTX. In this randomized study, patients received either ACTEMRA (4 mg/kg or 8 mg/kg, one infusion every four weeks) in combination with methotrexate or methotrexate alone. The results presented are from a planned 12-month analysis of a 2-year study. At 52 weeks, total Genant-modified Sharp Score change from baseline for the ACTEMRA 8mg + MTX, 4mg +MTX, and MTX alone groups were: 0.29, 0.34 and 1.1 respectively. The percentage of patients achieving no progression in total Genant-modified Sharp Score were 85%, 81% and 67%.The HAQ-DI AUC change from baseline, adjusted mean scores were: -144.1, -128.4 and -58.1 respectively. DAS28 clinical remission (

GlaxoSmithKline And Genmab Initiate Ofatumumab Rheumatoid Arthritis Phase III Programme

2011-05-23T14:00:00.000-07:00

GlaxoSmithKline (GSK) and Genmab A/S (OMX: GEN) announced the initiation of the Phase III programme with ofatumumab to treat rheumatoid arthritis (RA). The programme will commence with two studies (OFA110635/GEN410 and OFA110634/GEN411), which will be conducted outside the US, in two distinct patient populations. One study will be in patients who have had an inadequate response to methotrexate therapy; and the other in patients who have had an inadequate response to TNF-alpha antagonist therapy. Further studies to support the programme are planned for 2008.

Each study will evaluate the efficacy of ofatumumab in reducing the clinical signs and symptoms in RA patients after a single course of ofatumumab and comprises of a 24 week blinded period followed by a 120 week open-label period during which re-treatment will be studied. The primary endpoint in each study is ACR20 at 24 weeks.

"This brings us closer to our goal of broadening the treatment options for patients with this painful and debilitating disease" said Lisa N. Drakeman, Ph.D., Chief Executive Officer of Genmab. "From the data to date, we believe that ofatumumab has real potential. Now that Phase 3 studies are underway in multiple indications we are moving closer to realising this potential and bringing this important treatment to patients."

"We are very pleased that our collaboration with Genmab has progressed so that we can now move to the next step of the clinical trial programme," said Dr Moncef Slaoui, Chairman of Research and Development, GlaxoSmithKline.

Ofatumumab is an investigational, fully human, next generation monoclonal antibody that targets a unique epitope of the CD20 receptor on the surface of B-cells. This epitope is different than other anti-CD20 antibodies currently available or in development.

About the Trials:

OFA110635/GEN410 - Clinical efficacy and safety of ofatumumab in adult RA patients who have had an inadequate response to methotrexate

A total of approximately 250 patients who had an inadequate response to methotrexate therapy will be enrolled. In the double-blind period, patients will be randomised to receive two 700 mg doses of ofatumumab or placebo two weeks apart in addition to background methotrexate. Rescue treatment with nonbiologic disease modifying anti-rheumatic drugs (DMARDs) will be allowed from Week 16 in the double-blind period. All patients who complete the double-blind period without receiving rescue treatment will continue into the open-label period of the study. Re-treatment will be studied, starting at Week 24. Disease status will be measured every 4 weeks during the double-blind period and every 8 weeks during the open-label period.

OFA110634/GEN411 - Clinical efficacy and safety of ofatumumab in adult RA patients who have had an inadequate response to TNF-alpha antagonist therapy

A total of approximately 250 patients who had an inadequate response to TNF-alpha antagonist therapy will be enrolled. In the double-blind period, patients will be randomised to receive two 700 mg doses of ofatumumab or placebo two weeks apart in addition to background methotrexate. Rescue treatment with nonbiologic disease modifying anti-rheumatic drugs (DMARDs) will be allowed from Week 16 in the double-blind period. All patients who complete the double-blind period without rescue treatment will continue into the open-label period of the study. Re-treatment will be studied, starting at Week 24. Disease status will be measured every 4 weeks during the double-blind period and every 8 weeks during the open-label period.

About GlaxoSmithKline

GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

About Genmab A/S

Genmab is a leading international biotechnology company focused on developing fully human antibody therapeutics for unmet medical needs. Using unique, cutting-edge antibody technology, Genmab's world class discovery and development teams have created and developed an extensive pipeline of products for potential treatment of a variety of diseases including cancer and autoimmune disorders. As Genmab advances towards a commercial future, we remain committed to our primary goal of improving the lives of patients who are in urgent need of new treatment options. For more information on Genmab's products and technology, visit genmab.

GlaxoSmithKline Forward-Looking Statements

Under the safe harbor provisions of the US Private Securities Litigation Reform Act of 1995, the company cautions investors that any forward-looking statements or projections made by the company, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect the Group's operations are described under 'Risk Factors' in the Business and Prospects in the company's Annual Report on Form 20-F for 2006.

Genmab Forward-Looking statements

This press release contains forward looking statements. The words "believe", "expect", "anticipate", "intend" and "plan" and similar expressions identify forward looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with product discovery and development, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products obsolete, and other factors. Genmab is not under an obligation to up-date statements regarding the future following the publication of this release; nor to confirm such statements in relation to actual results, unless this is required by law.

Lubricant's Role In Keeping Joints Limber Comes Into Sharper Focus

2011-05-22T13:45:00.000-07:00

Using a method that allows precise measurement of the biomechanical properties of the hip joints in mice, researchers at Duke University's Pratt School of Engineering have found new evidence that an ingredient of joint fluid called lubricin plays a significant role in keeping joints limber.

The researchers say the finding offers the strongest evidence yet that treatments designed to increase levels of lubricin in humans may help stall the deterioration of arthritic joints.

The team found that the arthritic joints of mice lacking the gene that controls the production of lubricin show greater friction than do joints in normal animals. When observed at the molecular level, the surface of the mutant animals' joint cartilage also appears rougher and less stiff -- a finding that the researchers said suggests a loss of the cartilage's mechanical integrity without lubricin.

"Lubricin has been considered important, but the experiments had not been done," said Stefan Zauscher, a professor of mechanical engineering and materials science at the Pratt School. "This is the first look at the effects on biomechanics of lubricin's presence or absence."

Team member Jeffrey Coles, a Ph.D. student working in Zauscher's laboratory, presented the findings at the annual meeting of the Orthopaedic Research Society, in San Diego. The work was supported by the National Institutes of Health.

While lubricin had been suspected to play a role in reducing joint friction, earlier studies had focused on another constituent of joint fluid called hyaluronic acid. Injections of this material are frequently used as a treatment for osteoarthritis, the most common form of arthritis. However, the treatment seems to work primarily as an anti-inflammatory agent, Zauscher noted, doing little to prevent further joint damage.

Last year, Zauscher's group reported evidence that lubricin acts as a repellant boundary layer between joint surfaces, reducing friction by preventing contacts altogether rather than simply "greasing the wheels" pratt.duke/news/index.php?story=260.

Those results stemmed from the first examination of the changing molecular forces between a model joint and glass slide as the amount of lubricin in the solution between them increased.

Now, the researchers have applied a similar technique to the molecular-level study of mouse joints, comparing normal mice to those lacking the gene for lubricin. They used an atomic force microscope (AFM) to examine the cartilage found on the surface of the ball at the top of the thigh bone that fits into the hip socket of the mice.

AFM microscopes have a sharp tip that scans the surfaces of structures at the level of individual atoms and measures the force of molecular-level interactions. In this case, the team chemically modified the tip to imitate the chemical properties of joint cartilage.

The researchers used the modified tips to probe the surface of normal and lubricin-deficient joints, gaining measurements of the amount of friction between the two surfaces. They also obtained measurements of the roughness and stiffness of the cartilage surface.

When compared with mice that have normal joint cartilage, mice lacking lubricin showed two to three times the amount of friction and their joint surfaces were more than twice as rough. The stiffness of the joint cartilage in mutant mice also was reduced by a factor of five, the researchers found. They noted that these findings are consistent with the significant tissue degeneration in early osteoarthritis.

"It's clear from our findings that lubricin is important for protecting the structural integrity of joints," Coles said.

The researchers next will examine the effects of replacing lubricin on the joint surfaces of mutant mice. They are seeking a better understanding of how lubricin carries out its role as a boundary lubricant, leading perhaps to an improved treatment option for osteoarthritis. Preliminary evidence suggests that lubricin injections may prevent, or at least slow, further deterioration of joint cartilage in the arthritic mice.

Collaborators on the study included Farshid Guilak of Duke University Medical Center and Duke's Pratt School of Engineering; J. Cha and Gregory Jay of Brown University; and Matthew Warman of Case Western Reserve School of Medicine.

Contact: Kendall Morgan

Duke University

Reverse Shoulder A Final Option For Restoring Function

2011-05-21T13:30:00.000-07:00

Athough most artificial joints resemble the shape and structure of the joint they're designed to replace, one new prosthesis the reverse shoulder takes a different approach, reversing the position of the normal ball-and-socket design. The purpose of this anatomical flip-flop is to give you a shoulder that is stable enough to let you raise your arm, even if your rotator cuff is torn beyond repair, according to Cleveland Clinic's Arthritis Advisor.

"When we replace a shoulder joint, it's normally with a traditional, anatomically shaped design," says Joseph P. Iannotti, M.D., Ph.D., chairman of the department of orthopaedic surgery at Cleveland Clinic. "But this design only makes sense if the tears in your rotator cuff are repairable."

A working rotator cuff is the key to normal shoulder function since it's this group of four tendons encircling the shoulder that keeps the joint stable, holding the head of the humerous firmly against the curve of the scapula (glenoid cavity). Only when this head is stable can it act as an effective fulcrum, allowing the pull of your rotator cuff and deltoid muscles to raise your arm.

Loss of function

"As you age, it's not uncommon to develop a large tear in your rotator cuff," says Dr. Iannotti. "We often see tears in people in their 60s and 70s that may have been there for months or even years."

At some point, when a tear develops, the rotator cuff is unable to hold the humeral head within the socket, allowing it to slip out of place, hindering shoulder function. "Such tears can lead to pseudo or functional paralysis," says Dr. Iannotti. "Though your nerves are fully functional, you can no longer raise your arm to shoulder level."

If the tear is repairable, the shoulder muscles not too atrophied, and the shoulder has severe arthritis, your surgeon will likely recommend a traditional shoulder prosthesis whose design mimics the natural position of the humeral head (ball) and scapular depression (socket). This anatomic design is an effective solution as long as your repaired rotator cuff can provide adequate stability to the new joint.

"Some 20 to 30 percent of patients with significant rotator cuff tears and arthritis still have enough residual function to raise their arms to shoulder level before surgery, and are still good candidates for an anatomic prosthesis," says Dr. Iannotti.

Reverse-shoulder prerequisites However, if your tears are irreparable, the pain from arthritis is significant and, most importantly, you are unable to lift your arm to 90 degrees, then you may be a candidate for a reverse-shoulder procedure. Though the reverse shoulder prosthesis (made by DePuy, Tornier, Encore, and Zimmer) has been used clinically in Europe for more than two decades, it only received approval from the U.S. Food and Drug Administration in November 2004.

"Though I mostly recommend reverse shoulders for those over age 70, it can also make sense for younger patients who have a previous shoulder implant that has failed," says Dr. Iannotti, who has performed more than 120 of the procedures.

Candidates for a reverse shoulder must meet two other criteria good deltoid muscle function and a healthy glenoid bone. The importance of these is best explained by looking at the design of the reverse shoulder prosthesis.

Stable by design

As the name implies, the reverse shoulder flip-flops the normal position of the shoulder's ball and socket, putting a metal (titanium) stem topped with a plastic cup where the head of your humerus was and, on the other side, putting a metal plate and partial sphere (glenosphere) where the depression (glenoid cavity) on your scapula was. According to design engineers, this reversal changes the center of rotation within the joint, making the new head of the prosthesis inherently stable, regardless of the health of your rotator cuff.

With this design, good glenoid bone quality is a must because the bone must hold the screws which anchor the plate that holds the metal glenosphere. A functioning deltoid muscle is important since the new prosthesis depends upon this muscle for its arm-lifting power.

"As long as you have about 75 percent deltoid function, you'll be eligible for a reverse shoulder," says Dr. Iannotti.

Measured expectations

The range of motion you regain with a reverse shoulder will depend, in part, on how much function remains in your rotator cuff. "At a minimum, even with a little or no cuff function, you should be able to raise your arm to shoulder level," says Dr. Iannotti. "And those who retain at least partial function, especially in the posterior rotator cuff tendons, will often obtain 120 to 140 degrees of shoulder elevation."

Of course, getting to that point means a serious commitment to rehabilitation. The rehab program with a reverse shoulder is similar to that with an anatomic shoulder design, but it often can begin a bit sooner, since the shoulder's more innately stable design is less dependent on the health and healing of surrounding tissues.

Imperfect solution

Though a reverse shoulder can be a big help to certain people, it's far from an ideal solution. "The nature of the design puts a higher than normal load on the screws that are anchored into the glenoid process and, with repeated stress, can become loose and cause premature failure," explains Dr. Iannotti, who still views the reverse shoulder as a last-resort salvage solution in very selected patients.

"The reverse shoulder remains a complex procedure, for which there is not enough data to know long-term greater than 10-year results," says Dr. Iannotti. "What we do know is that, for a select group, it may be the best hope for more normal shoulder function."

Are You a Candidate?

If you experience or have one or more of the following, you may be eligible for a reverse shoulder procedure:

-- Severe shoulder arthritis with ongoing pain

-- Inability to raise extended arm to shoulder height

-- Irreperable large or massive rotator cuff tears

-- Healthy bone stock in scapula clavicle (glenoid cavity)

-- Functioning deltoid muscle

-- At least 65 years old, but younger if you've experienced failure of a previous shoulder replacement

Belvoir Media Group, LLC.

7820 Holiday Drive So., Suite 315

Sarasota, FL 34231

United States

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Using Statins To Potentially Treat Rheumatoid Arthritis

2011-05-20T13:15:00.000-07:00

Study finds statins have beneficial effect on rheumatoid arthritis cells in vitro
Statins, a class of drugs widely used to treat high cholesterol, have also recently been studied for their potential role in inflammation and other cell processes, including immune response. They have also been shown to induce apoptosis (cell death) in normal cells and tumor cells. Rheumatoid arthritis (RA) causes proliferation of synovial tissue, which lines the joints, but little is known about the effect of statins on this type of tissue. A study published in the February 2006 issue of Arthritis & Rheumatism (interscience.wiley/journal/arthritis) examined whether statins are able to induce apoptosis in synovial cells of patients with RA and found that they have potential as a novel way of treating the disease.

The activation and proliferation of synovial cells, which is thought to play a key role in RA, may be exacerbated when apoptosis of synovial cells is either insufficient or resistant to treatment. In the first study to demonstrate whether statins can induce apoptosis in synovial cells of RA patients, researchers led by Takao Nagashima of Jichi Medical School, Tochigi, Japan measured the effect in vitro of two statins, fluvastatin (a fat-soluble statin) and pravastatin (a water-soluble statin) on human synovial cells from patients with RA and osteoarthropathy. "In the present study, we demonstrated that fluvastatin induced apoptosis in synoviocytes from patients with RA, but not in those from patients with osteoarthropathy, suggesting that the apoptotic effect of fluvastatin is a mechanism for suppression of inflammatory arthritis such as RA by statins," the authors state.

They were also able to determine the pathway by which apoptosis occurred: the inhibition of protein geranygeranylation (a process involving the metabolism of certain proteins that is essential for proper cell function, including the survival of vascular smooth muscle cells) was shown to be necessary for apoptosis to occur in these cells. Specifically, the pathway involves inhibition of the geranylgeranylated protein RhoA/RhoA kinase, which has already been shown to be involved in apoptosis.

The researchers point out that the in vitro concentrations they used of the statins were much higher than amounts that would normally be prescribed to patients. Although they note that it is possible that in the human body relatively low, but sustained, blood levels of statins would exert an effect similar to that seen in vitro with higher concentrations and short incubation times, they acknowledge that the therapeutic effect of fluvastatins in patients remains to be determined.

The authors conclude: 'The induction of apoptosis in RA synovial cells by fluvastatin and the biologic antiatherosclerotic properties of the statins suggest that they may turn out to be ideal therapeutic agents in RA. Based on these results, we propose that the statins warrant clinical trials as potential modifiers of RA."

Article: "Apoptosis of Rheumatoid Synovial Cells by Statins Through the Blocking of Protein Geranlgeranylation," Takao Nagashima, Hitoaki Okazaki, Kazuo Yudoh, Hiroaki Matsuno, Seiji Minota, Arthritis & Rheumatism, February 2006; 54:2; pp. 579-586.

Contact: Amy Molnar

amolnarwiley

John Wiley & Sons, Inc./

CEL-SCI Study Shows CEL-2000 Vaccine Blocks Progression Of Rheumatoid Arthritis

2011-05-19T13:00:00.000-07:00

CEL-SCI Corporation (NYSE CVM) and their scientific collaborators announced that the Company's CEL-2000 vaccine demonstrated that it is able to block the progression of rheumatoid arthritis (RA) in a mouse model. The results were published in the scientific peer-reviewed Journal of International Immunopharmacology (online edition) in an article titled "CEL-2000: A Therapeutic Vaccine for Rheumatoid Arthritis Arrests Disease Development and Alters Serum Cytokine / Chemokine Patterns in the Bovine Collagen Type II Induced Arthritis in the DBA Mouse Model" with lead author Dr. Daniel Zimmerman. The study was co-authored by scientists from CEL-SCI, Washington Biotech, Northeastern Ohio Universities Colleges of Medicine and Pharmacy (NEOUCOMP) and Boulder BioPath.

CEL-2000, administered after disease (RA) symptoms had started, prevented, in a statistically significant manner, the further development of arthritic conditions, including joint swelling and deformation, bone and cartilage changes and was accompanied by serum cytokine alterations over the CEL-2000 treatment period with comparable or better activity than the well accepted etanercept (Enbrel®) therapy. The mode of action is very consistent with the findings of induction of IL-12 followed by interferon gamma and an inhibition of TNF-alpha and IL-17 production. TNF-alpha and IL-17 are both key cytokines for induction of the pathology seen in rheumatoid arthritis and TNF-alpha is the target of many current RA therapies such as Enbrel, Remicaid, and Humaria. The protection effect mediated by CEL-2000 treatment against RA was also demonstrated histologically with significant reductions in: 1) inflammation, 2) cartilage destruction, 3) bone resorption, and 4) pannus membrane formation in the synovial space compared to untreated controls.

Geert Kersten, Chief Executive Officer of CEL-SCI said, "These experimental results were achieved through a reduction of the inflammatory response that is known to attack the patients' joints. The mode of action of CEL-2000 in RA appears to be similar to our new investigational therapy for H1N1 hospitalized patients, as it attempts to avoid the excess TNF-alpha and other pro-inflammatory cytokines. We feel that this new data is encouraging both for this rheumatoid arthritis vaccine as well as in support of our H1N1 treatment currently under development."

In these studies, mice were injected with collagen to induce the autoimmune (RA) disease. Therapy with Enbrel or CEL-2000 was initiated after disease (RA) symptoms have been established and treatment continued for 28 days after the initiation of a significant, uniform, and measurable level of arthritic disease in groups of mice. CEL-2000 was administered only twice, however Enbrel had to be administered every other day for the 28 day study period (as indicated for Enbrel use). The extent of disease, as measured by deformation of foot joints (Arthritic Index (AI) score), of untreated animals and any improvements resulting from CEL-2000 and Enbrel treated animal were then compared. In another study, CEL-2000 was administered 5 times over a 70 day period and the animals were monitored for a total study period of 90 days. In each case, CEL-2000 treatment proved effective in blocking progression of disease (RA) with statistically significant reduction in AI score compared to controls. The CEL-2000 treatment was deemed safe and well tolerated without any reported adverse effects related to treatment.

The CEL-2000 treatment appeared to change the course of the immune response in the diseased (RA) animals, limiting the development of the destructive action of Th17 and tumor necrosis factor alpha (TNF-alpha). Analysis of serum levels of 21 cytokines/chemokines after 10 days of CEL-2000 treatment indicated reductions in the characteristic cytokine markers of rheumatoid arthritis, TNF-alpha and IL-17, as well as IL-6, and MCP-1. A number of cytokine changes were also seen with Enbrel treatment, but to a lesser degree than that seen with CEL-2000 treatment.

CEL-2000 may also offer a number of potential advantages over existing rheumatoid arthritis treatments, such as Enbrel. Data collected in the animal studies conducted with CEL-2000 demonstrated that CEL-2000 is an effective treatment against rheumatoid arthritis even with administration of many fewer treatments than for example Enbrel. CEL-2000 is also potentially a more disease-type specific therapy, should be significantly less expensive to manufacture, and finally, CEL-2000 could also be useful for patients who are not able to take or who may be unresponsive to other existing anti-arthritis therapies.

This research featured the multidisciplinary team of collaborators bringing to the project expertise of several different animal models of arthritis (Washington Biotech), long time association with modern molecular therapies and evaluation for RA (Bolder Biopath), experience with other LEAPS immunogens, and experience and expertise studying cytokines and with mechanistic studies of the LEAPS technology (NEOUCOMP), and peptide technologies (21st Century Biochemicals) to complement the expertise of the CEL-SCI researchers.

Rheumatoid arthritis treatments comprise an approximately $13 billion market. Enbrel, a leading rheumatoid arthritis treatment sold by Amgen and Wyeth, reported US sales in 2007 of about $3.2 billion. Enbrel is a soluble recombinant protein of a human TNF-alpha receptor linked to human IgG Fc. In some cases, human or humanized monoclonal antibodies specific against TNF-alpha have also been used for therapy in rheumatoid arthritis. These therapies remove or inactivate TNF-alpha, a natural human cytokine required in many immune functions for normal defenses.

CEL-SCI's rheumatoid arthritis vaccine CEL-2000 was discovered as part of work with the Company's ongoing research and development activities with its L.E.A.P.S.™ (Ligand Epitope Antigen Presentation System) technology. L.E.A.P.S. is a novel T-cell modulation platform technology that enables CEL-SCI to design and synthesize proprietary immunogens. Any disease for which an antigenic sequence has been identified, such as infectious, parasitic, malignant or autoimmune diseases and allergies, are potential therapeutic or preventive sites for the application of L.E.A.P.S. technology.

The concept behind the L.E.A.P.S. technology is to directly mimic cell-cell interactions and activate immune cells with synthetic peptides. The L.E.A.P.S. constructs containing the antigenic disease epitope linked to a immune-cell binding ligand (ICBL) can be manufactured by peptide synthesis or by covalently linking the two peptides. Depending upon the type of L.E.A.P.S. construct and ICBL used, CEL-SCI is able to direct the outcome of the immune response towards the development of T-cell function with primarily effector T-cell functions (T Lymphocyte; helper/effector T lymphocyte, type 1 or 2 [Th1 or Th2], cytotoxic [Tc] or suppressor [Ts]). Therefore, it would appear that the L.E.A.P.S. construct represents a chimeric peptide with bi-functional behavior.

About CEL-SCI Corporation

CEL-SCI Corporation is developing products that empower immune defenses. Its lead product Multikine is being readied for a global Phase III trial in advanced primary head and neck cancer. CEL-SCI is also developing an immunotherapy (LEAPS-H1N1-DC) to treat H1N1 hospitalized patients and a vaccine (CEL-2000) for Rheumatoid Arthritis using its L.E.A.P.S. technology platform. The LEAPS-H1N1-DC treatment involves non-changing regions of H1N1 Pandemic Flu, Avian Flu (H5N1), and the Spanish Flu as CEL-SCI scientists are very concerned about the creation of a new more virulent hybrid virus through the combination of H1N1 and Avian Flu, or maybe Spanish Flu. This investigational treatment is currently being tested in a clinical study at Johns Hopkins University. The Company has operations in Vienna, Virginia, and in/near Baltimore, Maryland.

When used in this report, the words "intends," "believes," "anticipated" and "expects" and similar expressions are intended to identify forward-looking statements. Such statements are subject to risks and uncertainties which could cause actual results to differ materially from those projected. Factors that could cause or contribute to such differences include, lack of regulatory clearance to proceed with clinical trials, an inability to duplicate the clinical results demonstrated in clinical studies that have been completed or that are initiated in the future, timely development of any potential products that can be shown to be safe and effective, unwillingness of regulatory authorities to engage in further regulatory dialogue, receiving necessary regulatory approvals, difficulties in manufacturing any of the Company's potential products, inability to raise the necessary capital, and the risk factors set forth from time to time in CEL-SCI Corporation's SEC filings, including but not limited to its report on Form 10- K for the year ended September 30, 2009. The Company undertakes no obligation to publicly release the result of any revision to these forward-looking statements which may be made to reflect the events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.

Source: CEL-SCI Corporation

View drug information on Enbrel.

MabThera for moderate-severe rheumatoid arthritis, good study results

2011-05-18T12:45:00.000-07:00

Roche together with development partners Genentech and Biogen Idec announced today that a Phase IIb clinical study of
MabThera/Rituxan (rituximab) met its primary endpoint of a greater proportion of MabThera-treated patients achieving an
American College of Rheumatology (ACR) 20 response at week 24, compared to placebo, in patients who were also treated with
methotrexate (MTX). In this study, patients with moderate-to-severe rheumatoid arthritis (RA) who received two infusions of
MabThera over a two-week period in combination with a stable dose of MTX experienced improved symptoms compared to patients
who received placebo and MTX. The benefit in the MabThera/Rituxan treated patients was present regardless of whether
additional corticosteroids were administered.

"The preliminary data from this latest study in rheumatoid arthritis confirms MabThera as a promising alternative to current
therapies available to patients with RA and are consistent with earlier data showing efficacy and safety of MabThera. As we
continue to explore and evaluate MabThera as a potential treatment for RA, we look forward to the results of ongoing analyses
which will be presented next year", commented Dr. Eduard Holdener, Head of Global Pharma Development, Roche.

This Phase IIb study, DANCER (Dose-Ranging Assessment iNternational Clinical Evaluation of
Rituximab in RA), was designed to evaluate the efficacy and safety of varying doses of MabThera/Rituxan in combination
with methotrexate in patients with active RA who currently have an inadequate response to methotrexate. The influence of a
short initial course of corticosteroids was also evaluated.

All regimens in the study were generally well tolerated. The reported rate of serious adverse events was not significantly
different than seen in previous studies of MabThera/Rituxan in RA. MabThera/Rituxan is also being studied in an additional
ongoing trial, REFLEX (Randomised Evaluation oF Long-term Efficacy rituXimab in RA)
in patients who have an inadequate response to anti-TNF alpha (tumour necrosis factor) therapies.

MabThera/Rituxan is a therapeutic antibody that selectively depletes B cells, which may play a key role in the inflammatory
cascade of RA. B cells are an important element in the immune system, helping the body to fight off infection. However in
autoimmune diseases like RA, the immune system acts abnormally leading to an attack on normal healthy tissue such as the
joints.

By depleting B cells, which are believed to be involved in maintaining the attack on healthy tissue, MabThera/Rituxan is
thought to break the cycle of rheumatoid arthritis disease. MabThera/Rituxan is already proven effective in RA following a
single course of therapy1,2.

There is a large unmet clinical need for RA treatments. Only around 50 percent of patients respond to and maintain treatment
with DMARD (disease modifying anti-rheumatic drugs) therapy long term. Data from existing clinical trials indicates that
MabThera/Rituxan is safe and well-tolerated in people with RA.

About the Study

DANCER (Dose-Ranging Assessment iNternational Clinical Evaluation of R in RA) is a
Phase IIb study evaluating the efficacy and safety of varying doses of MabThera/Rituxan and corticosteroids in combination
with a fixed dose of methotrexate in patients who have failed at least one disease-modifying anti-rheumatic drug (DMARD) and
are inadequately responding to methotrexate. A total of 465 patients from the United States, Canada, Europe, and Australia
were randomised in this multi-centre, randomised, double-blind, placebo-controlled study. DANCER included three different
dosages of MabThera/Rituxan (placebo; 2x500mg; 2x1000mg) and corticosteroid (placebo; i.v. 200mg; and i.v. 200mg + p.o.
570mg).

About MabThera/Rituxan

Unlike current RA treatments, MabThera/Rituxan is a therapeutic monoclonal antibody that selectively targets B cells, which
are believed to play a key role in the inflammatory cascade of the disease. By doing so, MabThera/Rituxan aims to break the
inflammatory cascade of RA - a series of reactions inflaming the synovia and leading to the cartilage loss and bone erosion
that is characteristic of the disease in which B cells are thought to play a key role. MabThera/Rituxan has been used for
over 7 years for the treatment of a form of lymphatic cancer called non-Hodgkin's lymphoma (NHL) with over 380,000 patients
treated to date.

About Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a progressive, systemic autoimmune disease characterized by inflammation of the membrane lining
in joints. This inflammation causes a loss of joint shape and function, resulting in pain, stiffness and swelling, ultimately
leading to irreversible joint destruction and disability. Characteristics of RA include redness, swelling, pain, and movement
limitation around joints of the hands, feet, elbows, knees and neck. In more severe cases of RA the eyes, lungs or blood
vessels may be involved. RA may also shorten life expectancy by affecting major organ systems and after 10 years, less than
50% of patients can continue to work or function normally on a day to day basis. RA is one of the most common forms of
autoimmune disease and affects more than 6 million people worldwide, up to 2 million of whom are in Europe.

ACR improvements

The ACR response is a standard assessment used to measure patients' responses to anti-rheumatic therapies, devised by the
American College of Rheumatology (ACR). It requires a patient to have a defined percentage reduction in a number of symptoms
and measures of their disease. For example, a 20 or 50 percent level of reduction (the percentage of reduction of RA
symptoms) is represented as ACR20, ACR50. ACR 20 indicates a 20 percent improvement in the number of swollen and tender
joints, as well as a 20 percent improvement in three of five categories: patient assessment, physician assessment, pain
scale, Health Assessment Questionnaire, and acute phase reactant (erythrocyte sedimentation rate or c-reactive protein) ACR50
response is exceptional for existing treatments and represents a significant improvement in a patient's condition. A 'Major
Clinical Response' is defined as a continuous ACR 70 maintained for at least 6 months.

About Roche

Headquartered in Basel, Switzerland, Roche is one of the world's leading research-intensive healthcare groups. Its core
businesses are pharmaceuticals and diagnostics. As a supplier of innovative products and services for the prevention,
diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people's health and quality
of life. Roche is number one in the global diagnostics market, the leading supplier of medicines for cancer and
transplantation and a market leader in virology. In 2003, the Pharmaceuticals Division generated 19.8 billion Swiss francs in
prescription drug sales, while the Diagnostics Division posted sales of 7.4 billion Swiss francs. Roche employs roughly
65,000 people in 150 countries and has R&D agreements and strategic alliances with numerous partners, including majority
ownership interests in Genentech and Chugai.

About Genentech

Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes biotherapeutics for
significant unmet medical needs. A considerable number of the currently approved biotechnology products originated from or
are based on Genentech science. Genentech manufactures and commercializes multiple biotechnology products directly in the
United States and licenses several additional products to other companies. The company has headquarters in South San
Francisco, California and is traded on the New York Stock Exchange under the symbol DNA. For press releases and additional
information about the company, please visit gene.

About Biogen Idec

Biogen Idec creates new standards of care in oncology and immunology. As a global leader in the development, manufacturing,
and commercialization of novel therapies, Biogen Idec transforms scientific discoveries into advances in human healthcare.
For product labelling, press releases and additional information about the company, please visit biogenidec.

All trademarks used or mentioned in this release are legally protected.

References:

1. Edwards J et al. Efficacy of B-cell targeted therapy with rituximab in patients with rheumatoid arthritis. New England
Journal of Medicine 2004;350:2572-81

2. Emery P et al. Efficacy and safety of rituximab at 2 years following a single treatment in patients with active arthritis.
Oral presentation ACR 2004.

Access To Psychological Support And Self-Management Courses Could Ease The Emotional Burden Of Arthritis/Rheumatism, Survey Says

2011-05-17T12:30:00.000-07:00

An online survey for World Arthritis Day (WAD), completed by over 3,600* respondents revealed that access to psychological support and self-management courses could help people with arthritis/rheumatism cope more effectively with their condition and achieve better quality of life. Healthcare professionals, people with rheumatic disease and their carers, who responded to the survey, highlight the importance of integrating psychological support into the standard treatment regime.

The survey, a project run by the European League Against Rheumatism (EULAR) Standing Committee of People with Arthritis/Rheumatism in Europe (PARE), was completed by people with arthritis/rheumatism, their carers and health professionals from over 50 countries across the world.

Ninety seven percent of people with rheumatism/arthritis and carers indicated that this condition affects them/people they care for emotionally and 5% of them said it may lead to depression. Despite of the scale of the problem only 35% of the survey respondents said they raise the emotional impact of their arthritis/rheumatism with their doctor.

Clinical data demonstrates that the quality of life of these people can be enhanced by introducing special coping strategies1. The majority of people with arthritis/rheumatism who responded to the survey saw the need for professional support: 85% emphasised that psychological support (psychotherapy, sessions with psychologists, treatments) should be included in the overall care and over a half of them would like to have access to self-management courses.

Similarly, health professionals are increasingly aware of the psychological impact of arthritis/rheumatism: 71% said they bring this problem up during a consultation, 33% said they refer their patients to the specialist treatment (e.g. psychotherapy) and 22% suggest a self-management course, if one exists in the given country.

"The main message coming out of the World Arthritis Day survey is the real need for a holistic approach in treating people with arthritis and rheumatism, ensuring the treatment paradigm covers all aspects of these conditions and not just the physical symptoms. This is clearly voiced by both patients and physicians and needs to be recognized and addressed within the structure of national healthcare systems" - said president of EULAR Executive Committee, Prof. Ferdinand C. Breedveld.

"Our survey clearly demonstrates that both people with arthritis/rheumatism and healthcare professionals recognize the importance of addressing psychological aspects of this condition. Yet, in many countries support is not available or limited. - said Sandra Canadelo, Chairperson of the Standing Committee of People with Arthritis/Rheumatism in Europe (EULAR) - This year, on World Arthritis Day, we hope that our call for better access to different forms of psychological support for people with arthritis/rheumatism will be heard by health policy makers on a national and international level."

The findings from the Think Positive survey correspond with the available clinical evidence. This evidence demonstrates that arthritis/rheumatism can have a debilitating effect on people's lives by restricting physical, psychological and social function. A half to two thirds of people with arthritis/rheumatism report lost social relationships, disrupted leisure activities and limitations in employment because of psychological problems2. In many cases some types of arthritis/rheumatism can be associated with depression and anxiety3.

Results from the Think Positive survey are reflected in the individual stories of people with arthritis/rheumatism who share personal experiences of coping with their conditions emotionally and finding the best way to a keep positive frame of mind. Their testimonials are available on WAD website worldarthritisday/

About the WAD survey

The World Arthritis Day survey is a project run by EULAR Standing Committee of People with Arthritis/Rheumatism in Europe (PARE). Every year the survey looks at different aspects of arthritis/rheumatism and generates useful statistics to support a call for better standards of treatment and care for people with arthritis/rheumatism. The "Think Positive" theme acknowledges the emotional impact of this condition and the need for better psychological support being offered to people with rheumatism/arthritis.

About self-management courses

Self-management courses are run by people with arthritis/rheumatism who have been especially trained to teach techniques which help people get greater control over their disease, increase their confidence and improve their quality of life. These sessions create forums during which people feel comfortable to share their experiences and learn from each other. They enhance dialog and relationship building with other people affected by arthritis/rheumatism.

About EULAR Standing Committee of People with Arthritis/Rheumatism in Europe (PARE)

The European League Against Rheumatism (EULAR) is the organisation which represents the patient, health professional and scientific societies of rheumatology of all the European nations. EULAR endeavours to stimulate, promote, and support the research, prevention, treatment and rehabilitation of rheumatic diseases.

The national organisations of people with arthritis/rheumatism across Europe work together via the EULAR Standing Committee of PARE. The EULAR Standing Committee of PARE brings together representatives of arthritis and other musculoskeletal user groups around Europe to work towards improving the quality of life for the more than 100 million people in Europe living with these conditions. The committee's vision is of people with arthritis and other musculoskeletal conditions in Europe being empowered to lead full and independent lives.

More information is available on the website worldarthritisday/ and eular/

References:

1 Covic T et al, The impact of passive coping on rheumatoid, Rheumatology 2000; 39: 1027 1030

2 Ryan S, The Psychological and Social Implications of Rheumatoid Arthritis, available at NHS library: library.nhs.uk/musculoskeletal/viewresource.aspx?resid=5218 accessed on 22.08.08

3 Abdel-Nasser et al, Depression and depressive symptoms in rheumatoid arthritis patients: an analysis of their occurrence and determinants, Rheumatology, Volume 37, Number 4, April 1998 , pp. 391-397(7)

Acknowledgement

The WAD 'Think Positive' survey is supported by an educational grant from Pfizer

Source: Birte Gl??esing

Ruder Finn Public Relations

Expanded Indications, Novel Targets Driving Activity In Autoimmune Disease Therapeutics

2011-05-16T12:15:00.000-07:00

Already a major
therapeutic disease sector accounting for drug sales in excess of $18
billion worldwide, the incidence of autoimmune disease in developed
countries is increasing. The impact of autoimmunity on patient
quality-of-life is well known, but it has only been in the last ten
years with the introduction of biological drugs capable of modulating
the immune cascade that effective therapies for this most intractable
family of diseases have become available. The result has been a drug
sector that has grown rapidly to include more than a half-dozen
products with annual sales exceeding $1 billion.

The past few years have been marked by expanded indications, creating
new treatment options for caregivers and their patients. But in spite
of these recent successes -- and in part because of them -- work to
identify and develop new therapeutic candidates has intensified.

As with virtually any drug with significant efficacy, side effects
remain a major issue. Much of the current wave of development
activity is focused on the search for new classes of autoimmune drugs
that achieve a therapeutic benefit with minimal side effects. These
approaches include drug candidates that target specific immune
response processes, such as inhibiting the action of adhesion
molecules or interfering with the migration of activated immune cells
from lymph nodes.

Arthritis, because of its market size and economic importance, is
often the therapeutic target for pipeline therapies in this sector,
while less prevalent disease segments benefit almost exclusively
through secondary or expanded indications. The outlook for the
psoriasis segment is closely linked to the commercial market for
arthritis treatment, due to the significant prevalence of psoriasis
patients to suffer from psoriatic arthritis.

The Greystone research study 'Autoimmune Disease Therapeutics'
analyzes approved and development-stage therapeutic drugs for six
major autoimmune disease segments, and includes forecasts, analysis,
descriptions and evaluations of current and probable future market
developments, technology issues, and business factors.

More information is available
here.

About Greystone

Greystone Associates is a medical and healthcare technology
consulting firm providing services in strategic planning, venture
development, product commercialization, and technology and market
assessment.

Greystone Associates

Cost Shifting May Make Arthritis Medications Too Expensive For Medicare Beneficiaries

2011-05-15T12:00:00.000-07:00

Biologic disease-modifying antirheumatic drugs (DMARDs) such as adalimumab, etanercept and infliximab are effective at reducing symptoms and slowing progression of rheumatoid arthritis (RA). These drugs act more quickly, require less laboratory monitoring, and are better tolerated than nonbiologic DMARDs, but they are also up to 100 times more expensive. Insurance plans differ greatly in their coverage of and cost sharing for biologic DMARDs, sometimes shifting a large portion of the cost of patients. A new study examined the cost-sharing structures for biologic DMARDs in Part D plans and the resulting cost burden to patients. The study was published in the June issue of Arthritis Care & Research.

In 2003, Congress created the Medicare Replacement Drug Demonstration (MRDD) to provide temporary drug insurance until the start of Medicare Part D in 2006. The MRDD, which ran September 2004 - December 2005, targeted low-income vulnerable Medicare patients with select conditions, including RA, who did not have comprehensive drug insurance coverage. This program had similar cost-sharing arrangements to Medicare Part D and evaluations showed that it reduced financial barriers and improved health outcomes. However, unlike the MRDD, Part D plans could place high-cost items such as biologic DMARDs in a specialty tier, where they are subject to higher patient cost sharing. There is concern that specialty tiering imposes a heavy financial burden on RA patients.

Led by Jennifer M. Polinski of Brigham and Women's Hospital in Boston, researchers followed almost 15,000 vulnerable, low-income patients who were enrolled in the MRDD as they transitioned into Part D in 2006. They grouped patients into one of three drug coverage options: enrollment in a Part D plan further stratified by a Medicare Advantage or stand-alone plan, other creditable coverage or unknown coverage. They examined the benefit design of each plan, as well as potential differences in beneficiaries' annual out-of-pocket costs for biologic DMARDs under three coverage scenarios.

They found that 81 percent of poor and disabled Medicare beneficiaries with RA who participated in the MRDD program had enrolled in Part D plans by July 2006. Compared with stand-alone Part D plans, Medicare Advantage plans offered lower deductibles, lower premiums, and were more likely to require copayments (which are fixed), rather than coinsurance (typically a percentage paid by the insured person pays after an insurance deductible has been exceeded). They also placed significantly fewer restrictions on biologic DMARD reimbursement. "In spite of the greater generosity and lesser restrictions of Medicare Advantage plans, the most sick and most financially needy patients enrolled in these plans less often than they did in stand-alone plans," the authors note.

Most patients enrolled in plans that placed biologic DMARDs on high-cost specialty tiers and used coinsurance proportions as high as 75 percent. The specialty tier was created to ensure that beneficiaries receiving high-cost biologic agents were not discriminated against in terms of cost sharing, but there is concern about the financial impact of this structure, especially the widespread use of high coinsurance. The study found that Part D plans that require coinsurance instead of copayments shift the financial burden of these high-cost medications from the plan to the patient and to Medicare. In plans where cost sharing is high (e.g. plans with high coinsurance), patients may delay or not even begin therapy due to the high cost; in plans with cost sharing that is steep but manageable (e.g. plans with high copayments) patients may begin therapy but then discontinue it when faced with paying the full cost of the medication out of pocket. "Neither scenario is optimal for patients who may benefit from biologic DMARDs," the authors point out.

Specialty tier and coinsurance resulted in estimated annual expenditures for patients that exceeded $4,000 despite drug insurance coverage and more Part D plans have adopted specialty tiering over time. In 2006, 60 percent of the national stand-alone plans used this system but by 2008, 87 percent were using it. Similarly, between 2006 and 2008 the number of plans charging 33 percent coinsurance increased more than five-fold. "Patients assume up to 28 percent and Medicare assumes more than 58 percent of the costs of biologic DMARDs in our scenarios, yet neither is in a position to sustain such financial burden," the authors conclude. "As more biologic DMARDs are approved and used for RA and more plans use the specialty tier system, both beneficiaries and Medicare face costs they may be increasingly unable to afford."

Article: "Impact of Medicare Part D on Access to and Cost Sharing for Specialty Biologic Medications for Beneficiaries with Rheumatoid Arthritis," Jennifer M. Polinski, Penny E. Mohr, Lorraine Johnson, Arthritis & Rheumatism (Arthritis Care & Research), June 2009.

Source:
Sean Wagner

Wiley-Blackwell

Krystexxa (pegloticase) Approved For Treatment Of Gout

2011-04-27T12:00:00.048-07:00

Krystexxa (pegloticase) has been approved by the FDA (Food and Drug Administration) for patients with gout who either did not respond or could not tolerate conventional therapy. Gout is the result of an excess of uric acid in the body, leading to needle-like crystals forming in the joints or soft tissue, causing swelling, pain, joint stiffness, heat and redness.

According to Badrul Chowdhury, M.D., director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA's Center for Drug Evaluation and Research, approximately 3% of patients with gout do not respond to conventional therapy - this drug offers an important new option for them.

There are an estimated three million adults with gout in the USA. 3% of thee million is about 90,000 patients.

Conventional therapy for gout involves administering medications that lower uric acid levels in the blood. Examples include xanthine oxidase inhibitors Zyloprim (allopurinol) and Uloric (febuxostat).

Krystexxa, an enzyme, metabolizes the uric acid into a harmless chemical that the human body expels through urine, thus lowering uric acid blood levels. The patient receives an intravenous infusion once every two weeks.

Two clinical trials, lasting six months each and involving 212 participants, showed the Krystexxa reduced uric acid levels in the blood, and also reduced deposits of uric acid crystals in joints and soft tissue.

However, 25% of the clinical trial participants experienced a severe allergic reaction to Krystexxa. Therefore, health care providers should administer a corticosteroid and an antihistamine before giving the patient Krystexxa, in order to minimize reaction risk. The trials also reported some other reactions, including nausea, injection site bruising, nasal passage irritation, chest pain, vomiting, and constipation.

As Krystexxa has not been studied on individuals with congestive heart failure, the FDA warns doctors to be especially careful with such patients.

The FDA informs that Krystexxa is being approved with a Risk Evaluation and Mitigation Strategy that includes a medication guide for patients and materials for healthcare providers to communicate the risk of severe infusion and allergic reactions.

Paul Hamelin R.Ph., President of Savient Pharmaceuticals, makers of Krystexxa, said:

KRYSTEXXA is the first-ever and only treatment approved by the FDA for adult patients who suffer with chronic gout that is refractory to conventional therapy. The clinical data have demonstrated that many patients treated with KRYSTEXXA 8 mg administered every two weeks can experience within six months of treatment significant positive clinical improvement reversing the course of this severe, crippling and debilitating disease.

A statistically significant proportion of patients in our pivotal clinical trials achieved a lowering of their serum uric acid level to a mean of 0.7 mg/dL and achieved a complete response for the resolution of tophi within the first six months of therapy. We believe that the approval of KRYSTEXXA is a significant step towards realizing our mission of transforming the lives of the patients in the U.S. suffering with chronic gout refractory to conventional therapy, as many of them finally have a treatment that gives them hope of reversing this severely debilitating disease.

Savient Pharmaceuticals expects Krystexxa to be available by prescription in the U.S. later this year and believes it is well advanced in its preparations for its U.S. launch.
What causes gout?
The levels of uric acid in your blood rise until the level becomes excessive (hyperuricemia), causing urate crystals to build up around the joints. This causes inflammation and severe pain when a gout attack happens.

When the human body breaks down chemicals called purines it produces uric acid. Purines can be found naturally in your body, as well as in food, such as organ meats, anchovies, asparagus, mushrooms and herring.

Most of the time uric acid dissolves and goes into the urine via the kidneys. However, if the body is producing too much uric acid, or if the kidneys are not excreting enough uric acid, it builds up. The accumulation results in sharp urate crystals which look like needles. They accumulate in the joints or surrounding tissue and cause pain, inflammation and swelling.

Surprisingly, hyperuricemia is commonly found in many people who never develop gout. Scientists are not completely sure what causes hyperuricemia. There is definitely a genetic factor because a person who has close relatives with hyperuricemia is more likely to develop it himself.

The following have been known to bring about a gout attack and may be contributory causes of gout:

obesity
heavy alcohol consumption, especially beer
a diet high in purine foods, such as seafood and meat, and meat organs
extremely low calorie diets
regular aspirin use
regular niacin use
regular use of diuretic medicines
medicines taken by transplant patients, such as cyclosporine
fast weight loss
chronic kidney disease
hypertension (high blood pressure)
psoriasis
tumors
myeloma
hemolytic anemia
lead poisoning
hypothyroidism
surgery
Kelley-Seegmiller syndrome
Lesch-Nyhan syndrome

Click here to read about gout in more detail.

Sources: FDA, Savient Pharmaceuticals

Written by

View drug information on Krystexxa; Uloric.

Cause Of Cartilage Degeneration In Osteoarthritis Discovered By Scripps Research Scientists

2011-04-27T12:00:00.047-07:00

The scientists describe their work in this week's Early Edition of the Proceedings of the National Academy of Sciences. In the study, the team shows how the loss of the protein HMGB2, found in the surface layer of joint cartilage, leads to the progressive deterioration of the cartilage that is the hallmark of osteoarthritis.

"We have found the mechanism that begins to explain how and why aging leads to deterioration of articular cartilage," says Scripps Research Professor Martin Lotz, M.D., a world-renowned arthritis researcher who led the study with Noboru Taniguchi, M.D., Ph.D., a senior research associate in his lab. "Our findings demonstrate a direct link between the loss of this protein and osteoarthritis."

Osteoarthritis typically begins with a disruption of the surface layer of cartilage. The cartilage surface layer, called the superficial zone, is the most important functionally of the four layers of cartilage present in joints. In normal joints the cartilage surface is perfectly smooth, enabling joints to slide across one another without friction. Once the cartilage of the superficial zone starts to deteriorate, though, osteoarthritis sets in, triggering an irreversible process that eventually leads to the loss of underlying layers of cartilage until bone begins to grind painfully against bone. Osteoarthritis most commonly affects the spine, temporomandibular joints, shoulders, hands, hips and knees.

"We knew that the first phase of osteoarthritis is the destruction of cartilage in the superficial zone," says Lotz, who has spent the past five years studying the role of HMGB2 in osteoarthritis. "Now we know that before this layer is destroyed, there is loss of the critical DNA binding protein HMGB2 and that this loss is directly related to aging."

The team found that the protein HMGB2 is uniquely expressed on the surface layer of cartilage in joints, where it supports the survival of chondrocytes, the cells that produce and maintain cartilage. Aging is associated with the loss of HMGB2 and an accompanying reduction or total elimination of chondrocytes in the superficial zone. The scientists provided further links between HMGB2 and osteoarthritis by breeding mice to be genetically deficient in HMGB2; these mice had an earlier and more severe onset of osteoarthritis.

The findings, made in collaboration with colleagues from Scripps Research, San Raffaele University in Milan, Italy, and Kagoshima University in Kagoshima, Japan, provide a promising avenue to explore the development of new osteoarthritis treatment options.

"If small molecules can be found to prevent or stop the loss of HMGB2, or conversely, to stimulate the production of this protein, then it is possible that osteoarthritis may one day either be prevented or reversed," Lotz says.

The discovery also will impact research on the use of stem cells in tissue regeneration. Because cartilage is unable to heal itself, scientists have been searching for ways to use stem cells to grow replacement cartilage in the lab that could be used to surgically replace damaged or non-existent cartilage. With the discovery of the link between HMGB2 and surface layer protein, scientists now have a clue about how they might be able to engineer the surface layer cartilage.

"As our population ages, osteoarthritis will become an ever-greater health issue," Lotz says. "Everyone eventually gets osteoarthritis; even those people who are not functionally impaired by the disease are found to have cartilage damage. And it all starts with the loss of cells in the superficial layer. We now have a starting point for potential prevention, diagnosis, and treatment."

In addition to Lotz and Taniguchi, co-authors of the paper, titled, "Aging-related loss of chromatin protein HMGB2 in articular cartilage is linked to reduced cellularity and osteoarthritis," are Beatriz Carames and Ulrich Ulmer from the Scripps Research Institute; Lorenza Ronfani and Marco E. Bianchi from San Raffaele University in Milan; and Setsuro Komiya from the Department of Orthopaedic Surgery, Kagoshima University in Japan.

This work was supported by the National Institutes of Health, and by grants from the Arthritis National Research Foundation and the Japan Orthopaedics and Traumatology Foundation, Inc.

About The Scripps Research Institute

The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Scripps Research is headquartered in La Jolla, California. It also includes Scripps Florida, whose researchers focus on basic biomedical science, drug discovery, and technology development. Scripps Florida is currently in the process of moving from temporary facilities to its permanent campus in Jupiter, Florida. Dedication ceremonies for the new campus will be held in February 2009.

Source: Keith McKeown

Scripps Research Institute

Success Of Hip Replacement Surgery May Be Determined By Genes

2011-04-27T12:00:00.046-07:00

The success of long term hip replacement surgery may lie in the genes, suggests research published ahead of print in the Annals of the Rheumatic Diseases.

The researchers analysed genetic variations in 312 people, just over half of whom (162) had problems after hip replacement in the 10 years following surgery.

Among those with symptoms, 91 had early signs of "aseptic loosening," which describes a condition in which the artificial joint comes loose and the surrounding bone begins to dissolve. The other 71 patients had deep-seated infection, which occurs when the body is unable to control infection caused by bacteria colonising the artificial implants.

DNA samples were taken from all participants to test for genetic variations in genes responsible for generating matrix metalloproteinase 1, or MMP1 for short, interleukin 6, and vitamin D synthesis.

MMP1 is an enzyme that breaks down collagen, the main protein found in bone and cartilage, while interleukin 6 is a chemical involved in bone metabolism and the immune response.

Vitamin D synthesis is important for strong healthy bones.

Variations in the interleukin 6
gene did not seem to have any effect. But those with variations in MMP1 were more than three times as likely to have aseptic loosening as those who did not carry the genetic variation.

And variations in the vitamin D receptor gene almost doubled the chances of bone dissolution and deep infection.

The authors conclude that if confirmed in other research, these findings could be used to predict long term success in patients undergoing hip replacement surgery. And they could also be used to develop targeted genetic treatments.

Contact: Emma Dickinson

BMJ-British Medical Journal

Exploring New Treatments To End Osteoarthritis

2011-04-27T12:00:00.045-07:00

Arthritis researchers from North America and Europe will convene in Chicago this week to present new osteoarthritis research that could lead to better ways to detect, treat, prevent and cure osteoarthritis (OA), which affects 27 million Americans. Hosted by the Arthritis Foundation, the Segal North American Osteoarthritis Workshop (SNOW) on March 25-27 will focus on specific forms of OA, such as those that follow joint trauma, obesity and the aging process.

Arthritis is the leading cause of disability in the United States, affecting 50 million adults. The most common form of this highly prevalent disease is OA - a serious, painful and potentially life-altering disease, mainly affecting hands, knees and hips.

According to the Arthritis Foundation, the prevalence of OA is expected to increase significantly in coming years due to longer life expectancies, the obesity epidemic, and the first of the 78.2 million baby boomers reaching the retirement age this year. In addition, half of all adults will develop symptomatic knee OA at some point in their lives and that risk increases with obesity to two of every three obese adults.

"Findings presented at this workshop have the potential to significantly improve the outlook in osteoarthritis," says Arthritis Foundation Vice President of Research, Dr. John A. Hardin. "The goal of the conference is for participants to identify priority interventions that could be tested in a trial in the near future."

The following sessions will be presented at the conference:
Pathophysiological mechanisms in distinct forms of OA
Identifying the targets for therapeutic interventions for OA that are ready to be tested now
Partnerships with the Arthritis Foundation that can enhance efforts to solve OA
Advancing the care of patients with OA
Potential new interventions for OA
Recommendations for clinical trials for new interventions for OA that can be undertaken now

Research into the underlying causes of arthritis has been a high priority of the Arthritis Foundation over the past six decades. During that time, the organization has funded more than $400 million in research grants to thousands of scientists, resulting in better diagnostic tools, a greater understanding of the genetics involved in disease development, and the discovery of new treatments.

Source:

Carol Galbreath

Arthritis Foundation

Is rheumatoid arthritis becoming milder?

2011-04-27T12:00:00.044-07:00

Study affirms improving trend in the course of disease activity over the last decade, coinciding with more aggressive treatment strategies -

Rheumatoid arthritis (RA) is a chronic inflammatory disease, marked with joint pain and erosion. The course of RA can vary considerably, from mild to crippling, and is difficult to predict. On the strength of patient case histories and clinical trials, rheumatologists have suggested that the majority of today's RA patients are suffering less severe symptoms and less functional disability compared with RA patients in past decades.

Is the course of RA becoming milder? If so, why? Intrigued by these questions, researchers in The Netherlands decided to seek out the answers through a rigorous investigation. Published in the September 2005 issue of Arthritis & Rheumatism (interscience.wiley/journal/arthritis), their findings indicate a positive trend. "Patients with early RA presenting in recent years have less severe disease activity at presentation, as well as a more favorable course of their disease, compared with patients in earlier years," states the study's leading author, Paco M. J. Welsing, MSc.

What is the reason for this improving trend? Welsing and his colleagues found no clear, conclusive cause, and even uncovered some contradictory evidence. However, the team found a concurrent tendency toward a shorter duration of symptoms at the time of diagnosis and more aggressive use of drug therapy--for instance, methotrexate, today's preferred disease-modifying anti-rheumatic drug (DMARD) and/or prednisone--over the course of the disease.

The study included all newly diagnosed, early RA patients enrolled in the department of rheumatology clinic of Radboud University Nijmegen Medical Centre since 1985. Patients were divided into four groups based on the date of enrollment. Patients enrolled between 1985 and 1990 (167 total) comprised Group 1. Patients enrolled between 1990 and 1995 (132 total) comprised Group 2. Patients enrolled between 1995 and 2000 (114 total) comprised Group 3. And patients enrolled between 2000 and 2005 (112 total) comprised Group 4. In all groups, the majority of patients were women. The mean age at the time of enrollment was 54 years for Group 1; 55 years for both Groups 2 and 3; and 57 years for group 4.

Researchers set out to compare disease activity and functional disability among the groups over a 5-year progression (but 4-years, maximum, for Group 4). They also compared treatment strategies among the groups. All patients were assessed for signs of RA activity--namely, swelling and tenderness--in 28 joints every 3 months, a laboratory measure for inflammation and a measure of general well being by the Disease Activity Score 28 (DAS28). All patients were assessed for functional disability--covering difficulties with walking and conducting everyday activities--using the Health Assessment Questionnaire disability index (HAQ DI) every 6 months. In addition, all patients were periodically evaluated for pain in general.

The DAS28 scores at baseline and over the course of the study were consistently lower, indicating milder disease activity, in the more recent groups--that is, patients diagnosed with RA within the last ten years. At the 5-year culmination, the DAS28 scores were lowest in the most recent, complete group--Group 3, patients diagnosed between 1995 and 2000--compared with both Group 2 (1990-1995) and Group 1 (1985-1990). The average disease activity over time per patient showed similar trends of improvement. The average DAS28 score improved from 4.1 to 3.4 from the Group 1 to Group 3.

However, the HAQ DI scores at baseline and over time were not lower among patients enrolled later in the study, and even showed some evidence of a worsening trend. "This contradictory result may be partly a distinction between measures of physical examination, laboratory results, and patient-assessed outcomes," notes Welsing, "which can be influenced by internal standards or attitudes of patients."

Researchers did find a correlation between more aggressive treatment strategies and milder disease activity in the more recent groups of patients. While suggesting the effectiveness of early treatment with methotrexate, for instance, and/or prednisone for managing RA's symptoms and destructive progression, this connection calls for further investigation.

Article: "Is the Disease Course of Rheumatoid Arthritis Becoming Milder? Time Trends Since 1985 in an Inception Cohort of Early Rheumatoid Arthritis," Paco M. J. Welsing, Jaap Fransen, and Piet L. C. M. van Riel, Arthritis & Rheumatism, September 2005; 52:9; pp. 2616-2624.

John Wiley & Sons, Inc.

interscience.wiley

Treating Osteoarthritis With Coxibs And NSAIDs

2011-04-27T12:00:00.043-07:00

In an Editorial, to be published in the international journal Osteoarthritis and Cartilage (intl.elsevierhealth/journals/joca/), published by Elsevier, a panel of arthritis research experts has recommended that coxibs and nonsteroidal anti-inflammatory drugs (NSAIDs) must remain a significant part of the tool kit used in treating osteoarthritis (OA). The Editorial summarizes the outcomes of an international workshop organized by the Osteoarthritis Research Society International (OARSI) and the International COX-2 Study Group. The authors urge that an evidence-based approach must be taken when making recommendations to patients.

OA, the most common form of arthritis, is a major medical problem. It has been estimated that over 20 million Americans are afflicted with OA, and that number will rise to 40 million by the year 2020. Controversy now exists as to the safest and most efficacious way of treating the disease, particularly with respect to use of NSAIDs, both non-selective and selective (so-called COX-2 selective agents or coxibs). Adverse reactions related to the gastrointestinal tract, particularly with the non-selective NSAIDs, have been described; more recently, concerns have been expressed related to the cardiovascular system with both groups of agents.

A recent scientific statement from the American Heart Association (AHA) made recommendations with regard to the treatment of OA.1 A number of these recommendations are challenged in the Editorial2 in Osteoarthritis and Cartilage, with particular concern about their impact on appropriate use of these agents.

The Editorial questions the recommendation made in the AHA statement which described a stepped care approach to pharmacologic therapy for musculoskeletal diseases. The Editorial strongly recommends that several aspects of the AHA statement be reconsidered. For example, it urges that the AHA withdraw their non-evidence-based recommendations that high-dose aspirin be administered alone as a first line therapy for patients with chronic pain and arthritis.

Dr Roland W. Moskowitz, Professor of Medicine at Case Western Reserve University/University Hospitals of Cleveland, lead author of the Editorial comments, "Careful review of the pros and cons of using these agents, and the situations in which they are most safely and effectively used, is required to help us understand how best to take advantage of their availability".

The input by the OARSI/COX-2 International Study Group provides evidence-based background and guidance that will be of help to physicians, and to patients, in the use of these important commonly used agents.

Please see the article for additional information including author affiliations, financial disclosures, funding and support etc.

References:

1. E.M. Antman, J.S. Bennett, A. Daugherty, C. Furberg, H. Roberts, K.A. Taubert, Use of nonsteroidal antiinflammatory drugs. An update for clinicians: a scientific statement from the American Heart Association, Circulation. 2007;113:2906-2913.

2. R.W. Moskowitz, S. Abramson, F Berenbaum, L.S.Simon, M. Hochberg, Coxibs and NSAIDS -- Is the air any clearer? Perspectives from the OARSI international COX-2 workshop 2007, Osteoarthritis and Cartilage. 2007;15:849-856.

About OARSI

The Osteoarthritis Research Society International (OARSI) is a non-profit scientific professional organization that promotes and encourages fundamental and applied research in osteoarthritis. It is the only worldwide organization with the sole focus on OA (oarsi). Osteoarthritis and Cartilage is an international journal, owned by OARSI, and published on their behalf by Elsevier Ltd. The Journal is highly cited, being the top ranked orthopedics journal by impact factor (according to Thomson Scientific's Journal Citation Reports -- 2007). It is also widely read -- over 186,000 full-text papers from the Journal were downloaded via ScienceDirect in 2006.

About Elsevier

Elsevier is a world-leading publisher of scientific, technical and medical information products and services. Working in partnership with the global science and health communities, Elsevier's 7,000 employees in over 70 offices worldwide publish more than 2,000 journals and 1,900 new books per year, in addition to offering a suite of innovative electronic products, such as ScienceDirect (sciencedirect/), MD Consult (mdconsult/), Scopus (info.scopus/), bibliographic databases, and online reference works.

Elsevier (elsevier/) is a global business headquartered in Amsterdam, The Netherlands and has offices worldwide. Elsevier is part of Reed Elsevier Group plc (reedelsevier/), a world-leading publisher and information provider. Operating in the science and medical, legal, education and business-to-business sectors, Reed Elsevier provides high-quality and flexible information solutions to users, with increasing emphasis on the Internet as a means of delivery. Reed Elsevier's ticker symbols are REN (Euronext Amsterdam), REL (London Stock Exchange), RUK and ENL (New York Stock Exchange).

Source: Ian Salusbury

Elsevier

New Genes Implicated In Rheumatoid Arthritis

2011-04-27T12:00:00.042-07:00

Researchers continue to search for genetic clues into rheumatoid arthritis (RA), a chronic inflammatory joint disease. While its specific cause is not yet known, RA has been linked to an inherited susceptibility. Interestingly, despite its strong genetic component, RA's occurrence among siblings seems to be random.

In the quest to identify disease-specific gene expression profiles in patients with RA, researchers at the University of Michigan Medical Center turned to an ideal population: genetically identical, disease-discordant twins. The July issue of Arthritis & Rheumatism (interscience.wiley/journal/arthritis) highlights the results of their state-of-the-art genetic analysis.

Increasing evidence over the past several years indicates that B-lymphocytes play a central role in RA's development. In this study, microarray analysis was applied to lymphoblastoid B cell lines (LCLs) from 11 pairs of monozygotic twins, all with one healthy and one RA-affected twin. A revolutionary DNA technology, microarray can be used to not only compare gene expression in two different tissue samples, but to examine the expression of thousands of genes at once. The researchers extracted complementary DNA from the cells of every twin, labelled samples with fluorescent dye to distinguish RA cells from disease-free cells, and hybridized each on a 20,000-gene chip. Then, using immunohistochemistry and real-time polymerase chain reaction, they confirmed the expression of the most significantly over-expressed genes in synovial tissues. In addition, they compared gene expression in synovial tissue of the RA patients with gene expression in synovial tissue of patients with osteoarthritis (OA).

Between the disease-discordant twins, minor yet measurable differences were detected in the expression of 1,163 transcripts, representing 827 uniquely named genes. Of this total, 3 genes were significantly over-expressed in the cells of RA patients relative to their healthy co-twins. The most significantly over-expressed gene was laeverin, a newly discovered enzyme that works to degrade proteins. The second most significantly over-expressed gene was 11?-hydroxysteroid dehydrogenase type 2 (11?-HSD2), a steroid pathway enzyme linked to inflammation and bone erosion. This gene was also found over-expressed in the synovial tissue of OA patients. The third most significantly over-expressed gene was cysteine-rich, angiogenic inducer 61 (Cyr61), well-established for its role in the formation of new blood vessels.

"Our findings provide the first evidence that laeverin is abundantly expressed in synovial tissue," notes the study's leading author, Joseph Holoshitz, M.D. "11?-HSD2 and Cyr61 have not previously been directly implicated in RA," he adds. Uncovering 3 new genes with a clear abundance in RA, this study supports the promise of microarray analysis to not only provide further insights into the genetic components of this inflammatory disease, but also to help identify candidates for therapeutic intervention.

Article: "Identification of Genes Modulated in Rheumatoid Arthritis Using Complementary DNA Microarray Analysis of Lymphoblastoid B Cell Lines from Disease-Discordant Monozygotic Twins," Christian S. Haas, Chad J. Creighton, Xiujun Pi, Ira Maine, Alisa E. Koch, G. Kenneth Haines, III, Song Ling, Arul M. Chinnaiyan, and Joseph Holoshitz, Arthritis & Rheumatism, July 2006, (DOI: 10.1002/art.21953).

Contact: Amy Molnar

John Wiley & Sons, Inc.

Cartilage Discovery Offers Arthritis Hope

2011-04-27T12:00:00.041-07:00

Scientists have revealed the intricate structure of cartilage in what they hope will provide clues to how the crippling joint disease osteoarthritis might one day be treated.

The disease, which affects more than five million people in the UK, is caused by the wear and tear of the smooth, hard cartilage tissue that covers the ends of bones allowing them to glide over one another at the joint.

Scientists have long known that cartilage gets its strength from interlocking millimetre-long collagen fibres that work in a similar way to the load-bearing steel rods in reinforced concrete.

But the precise structure of these fibres or 'fibrils' has remained a mystery for more than 40 years, so hindering any progress towards the development of potential therapies.

Now, a team from The University of Manchester has used sophisticated electron microscope techniques to uncover the molecular structure of the thinner of the two types of collagen fibrils.

Professor Karl Kadler, who led the research in the Faculty of Life Sciences, said: "The ability of cartilage to withstand cycles of compression and relaxation is directly attributable to the collagen fibrils.

"Osteoarthritis occurs when the fibrils are disrupted or lost - just like concrete without the steel, the cartilage becomes mechanically weak and susceptible to wear and tear.

"Eventually, the cartilage breaks down altogether and sufferers experience severe pain as the two ends of the bones rub against each other."

The team's findings - published in the journal Proceedings of the National Academy of Sciences - also explain why mutations in cartilage collagen genes cause osteoarthritis.

"Without a detailed understanding of the structure of these fibrils, a treatment that prevents them deteriorating would always prove elusive," said Professor Kadler.

"This research, while just a beginning, at least establishes some basic scientific facts that could prove useful in future studies on osteoarthritis and related conditions."

The next stage of the team's work will be to determine the structure of the thicker fibrils and examine how collagen cells manage to produce these relatively large fibrous structures which are 1,000 times their own size.

Once scientists understand how the fibrils form and develop in healthy cartilage, they can then investigate what happens when things go wrong in diseases like osteoarthritis.

Osteoarthritis (OA) is the most common form of arthritis affecting an estimated 5.2 million people in the UK (source: Arthritis Research Campaign).

OA commonly affects the hands as well as the spine and large weight-bearing joints such as the hips and knees and less commonly the feet and ankles.

There is currently no cure for OA. Symptoms are relieved by the use of painkillers, anti-inflammatory drugs or local injections of glucocorticoid (a hormone steroid) or hyaluronan. In severe cases, joint replacement surgery may be necessary.

Contact: Aeron Haworth

University of Manchester

Cod Liver Oil really can slow the onset of osteoarthritis - proof

2011-04-27T12:00:00.040-07:00

Cardiff University (Wales, UK)

Experts reveal 'Granny's remedy' could hold key to cutting waiting lists, saving the NHS millions

Scientists from Cardiff University, UK, today (12th February 2004) revealed new clinical data showing that Cod Liver Oil really is effective in slowing the destruction of joint cartilage in patients with osteoarthritis.

The groundbreaking clinical study was led by Professor Bruce Caterson and Professor John Harwood of Cardiff University, and Professor Colin Dent, Orthopaedic Consultant, University of Wales College of Medicine.

For the first time ever, the clinical study provides unique human evidence (in vivo) of the effectiveness of Cod Liver Oil in the management of osteoarthritis.

The trial shows that 86% of pre-operative patients with arthritis, who took Cod Liver Oil capsules daily, had absent or significantly reduced levels of the enzymes that cause cartilage damage compared to 26% of those given a placebo oil capsule. In addition, the result showed a marked reduction in some of the enzymes that cause joint pain, in those patients taking the Cod Liver Oil.

According to surgeons, the findings could hold the key to reducing the number of knee and hip replacements carried out in the UK each year thereby shortening NHS waiting lists for joint replacement surgery. The estimated direct cost of arthritis to the health and social services is approx. ?5.5 billion annually.

Speaking at a press conference held at the Royal College of Surgeons in London, Professor Caterson said:

'This breakthrough is hugely significant because it demonstrates the efficacy of a dietary intake of Cod Liver Oil in patients with osteoarthritis taken prior to their joint replacement surgery. The data suggests that Cod Liver Oil has a dual mode of action, potentially slowing down the cartilage degeneration inherent in osteoarthritis and also reducing factors that cause pain and inflammation.

'What these findings suggest is that by taking Cod Liver Oil, people are more likely to delay the onset of osteoarthritis and less likely to require multiple joint replacements later in life.

'To put this into perspective, it is highly likely that if the Queen Mother had taken Cod Liver Oil as a young adult, she may have needed her first hip replacement much later on in life.'

v
The Trial

For the Cardiff University study, 31 patients on an NHS waiting list were recruited 10-12 weeks prior to total knee joint replacement surgery. Half of the patients were given two daily capsules containing 1000mg Extra High Strength Cod Liver Oil and half given placebo capsules.

At the time of surgery, samples of cartilage and joint tissue were taken from the knee joint and subjected to analysis.

Cartilage is the 'gristle' that cushions bones and prevents them from grinding against each other. Loss of cartilage leads to osteoarthritis, the painful and disabling condition, which caused more than 2 million people in the UK to visit their GP in the past year and the major reason for joint replacement surgery.

Impact of the study

Professor Colin Dent commented:

'Patients resort to joint replacement surgery when the symptoms and pain of their arthritis becomes unbearable. Cod Liver Oil can counteract these symptoms and if you can switch off the cartilage destruction and pain then surgery may not be necessary. We're very excited by this latest trial.'

Professor Caterson adds:

'I didn't think I'd be part of such a big breakthrough in my lifetime. Through fate and luck we've found a way of slowing down the progression of osteoarthritis. And it turns out to be a very affordable and safe treatment, a treatment that will impact on many people's lives.

'Our results also suggest that people who have suffered sporting injuries, that predispose them to the early onset of osteoarthritis (e.g. meniscal tears or cruciate ligament rupture) should consider taking Cod Liver Oil to slow the progression of their disease.'

These finding are particularly welcome for sufferers of osteoarthritis, many of whom are concerned about the adverse side effects, commonly associated with prescription drugs (Non Steroidal Anti Inflammatory Drugs).

Fergus Logan, chief executive of the Arthritis Research Campaign, which funded the pilot study said:

'These findings provide further proof that taking Cod Liver Oil or eating lots of oily fish slows down cartilage destruction in osteoarthritis, which is great news for those people who have the condition or worry about developing it, and who want to do something positive to help themselves.'

Professor Colin Dent concludes, 'This is where science and old wives' tales coincide. Our findings are consistent with advice that taking Cod Liver Oil in early adulthood could prevent the onset of osteoarthritis and would reduce the harmful symptoms associated with the disease.'

The findings from this study will be published in a medical journal later this year.

For more information:

Professor Bruce Caterson

Tel: 44-29-2087-4595

Email: Catersoncardiff.ac.uk

Professor John Harwood

Tel: 44-29-2087-4108

Email: Harwoodcardiff.ac.uk

Contact: Andrew Weltch

WeltchAcardiff.ac.uk

44-29-2087-5596

Inflammation elevates risk of cardiac death in rheumatoid arthritis patients

2011-04-27T12:00:00.039-07:00

Mayo Clinic epidemiologists have found that the systemic inflammation characterizing rheumatoid arthritis may be to
blame for the increased risk of cardiovascular death in patients with the disease.

"We believe that inflammation is a strong risk factor for cardiovascular disease among rheumatoid arthritis patients," says
Hilal Maradit Kremers, M.D., lead study investigator and research associate in the Mayo Clinic Department of Health Sciences
Research.

Rheumatoid arthritis patients have a significantly increased risk of dying of a heart condition if they have swelling in the
large joints, rheumatoid vasculitis (inflammation of the blood vessels), rheumatoid lung disease or a high erythrocyte
sedimentation rate (a blood test commonly known as ESR that measures level of inflammation in the body), report the
investigators in the March issue of Arthritis & Rheumatism (rheumatology/publications/ar).

"Our previous research showed that rheumatoid arthritis patients have a higher risk of early death than others and that these
deaths are mostly due to cardiovascular disease," says Sherine Gabriel, M.D., the study's senior author and Mayo Clinic
rheumatologist, epidemiologist and chair of the Department of Health Sciences Research. "We suspect that systemic
inflammation promotes this risk. Our findings support this hypothesis."

The exact means by which the inflammation in rheumatoid arthritis can lead to heart disease is unclear, say the Mayo Clinic
investigators, who indicate this is currently under study. The investigators hypothesize that if the degree of a rheumatoid
arthritis patient's inflammation can be closely monitored and kept under strict control, the risk of death by heart condition
may decrease. This hypothesis is also the subject of ongoing research.

The study was conducted using the resources of the Rochester Epidemiology Project (mayoresearch.mayo/mayo/research). The Mayo
Clinic researchers followed a group of 603 Rochester residents diagnosed with rheumatoid arthritis between Jan. 1, 1955 and
Jan. 1, 1995. The researchers collected detailed information about all study subjects' cardiac events and their
cardiovascular risk factors, such as diabetes, blood pressure, cholesterol, body mass index and smoking. They also collected
information on indicators of systemic inflammation and rheumatoid arthritis disease severity, such as rheumatoid factor
positivity, ESR, joint swelling, radiographic changes, rheumatoid arthritis nodules, rheumatoid arthritis complications,
rheumatoid arthritis treatments and disease duration. In addition, the researchers collected information on comorbitities,
the presence of additional diseases. All patients were followed until death, migration from Rochester or Jan. 1, 2001.

The paper detailing these findings is entitled "Cardiovascular Death in Rheumatoid Arthritis: A Population-Based Study."

Note for reporters: As the subjects in which the present analysis was conducted 1) have no direct patient relationship with
the investigators and 2) participated in this study under strict confidentiality agreements, the participants are not
available for news media interviews. The lead investigator, Dr. Gabriel, is available to speak to news media.

To obtain the latest news releases from Mayo Clinic, go to mayoclinic/news. MayoClinic (mayoclinic) is available as a resource for your health stories.

Contact: Lisa Lucier

newsbureaumayo

507-284-5005

Mayo Clinic

mayo

Addex Drug Candidate Effective In Osteoarthritis Pain Model

2011-04-27T12:00:00.038-07:00

Allosteric modulation company Addex Pharmaceuticals Ltd. (SWISS: ADXN) announced that its preclinical drug candidate ADX71943 was effective in a model of osteoarthritis pain. ADX71943 is a potent and selective positive allosteric modulator of gamma-aminobutyric acid subtype B (GABA-B) receptors. GABA-B receptors mediate the slow, prolonged physiological effects of the inhibitory neurotransmitter GABA and are implicated in pain processing. Phase I clinical testing is scheduled to start by the end of 2010.

"We believe the allosteric mechanism of ADX71943 is the key factor in the differentiated tolerability and lack of tolerance development observed in these preclinical studies. We look forward to testing this compound in humans, where we hypothesize that this product could provide not only a novel treatment for osteoarthritis pain, but also an important opioid-sparing therapy for other chronic pain indications," Addex CEO Vincent Mutel said.

The effects of ADX71943 on mechanical hyperalgesia (increased pain sensitivity) and mechanical allodynia (pain produced by a normally innocuous stimulus) were assessed in the monosodium iodoacetate (MIA) model of osteoarthritis, a model of chronic nociceptive pain. ADX71943 significantly reduced mechanical hyperalgesia and showed a trend toward reducing mechanical allodynia after both acute and sub-chronic (8 days) dosing. Statistically significant antihyperalgesic activity was observed on the first day and was maintained on day 8, despite increased pain severity.

A maximal effect of ADX71943 was already achieved with the lowest dose tested (1 mg/kg). The efficacious plasma concentration (corresponding to 1 mg/kg) was approximately 30-50 ng/mL. Importantly, no development of tolerance was observed during the eight day treatment period.

Addex reported previously that ADX71943 is orally efficacious in rodent models of inflammatory pain (formalin test and Complete Freund's Adjuvant- induced hypersensitivity) and visceral pain (acetic acid-induced writhing). ADX71943 also displays an improved tolerability profile with reduced side effects compared to baclofen.

Baclofen, a marketed generic orthosteric GABA-B receptor agonist, has shown analgesic effects in animal models of inflammatory and neuropathic pain. There also is some evidence of analgesic activity of baclofen in patients with neuropathic and cancer pain, although its use in patients is limited by CNS side effects.

Source:

Addex Pharmaceuticals

VGX Pharmaceuticals Receives FDA Clearance To Commence Clinical Trials Of VGX-1027, A Novel Oral Drug With Potent Anti-inflammatory Activity

2011-04-27T12:00:00.037-07:00

VGX Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) accepted the Investigational New Drug (IND) application for its lead anti-inflammatory compound, VGX-1027. VGX-1027 is an orally active, small molecule compound that has shown preclinical efficacy against various inflammatory diseases including Rheumatoid Arthritis (RA) and Type 1 diabetes (T1D).

VGX-1027 is the first of a new class of immune modulators that inhibits the production of several pro-inflammatory cytokines, which are responsible for the damaging effects of inflammatory diseases. Preclinical studies have shown that VGX-1027 is effective in inhibiting these cytokines in cell cultures. They have also demonstrated the product's efficacy in animal models for several diseases including RA, T1D, psoriasis, and colitis. Its main mechanism of action is the inhibition of NF-kB and the early transient inhibition of P38 MAP kinase signaling pathways.

Inflammatory diseases including RA, T1D, psoriasis, and colitis represent major medical problems. In the U.S. alone, over 2.7 Million people suffer from rheumatoid arthritis. An additional 1 Million Americans suffer from type 1 diabetes, which can be fatal if untreated.

Several blockbuster therapeutic agents dominate the multi-billion dollar RA drug market. However, all of these agents require injection into a patient's muscle or skin. VGX-1027 offers a distinct advantage over such products because it can be taken as a once-a-day pill. There are very few treatment options available for T1D patients other than insulin, which requires daily injections.

"VGX looks forward to promptly initiating Phase I clinical trials for VGX-1027, which has several potential advantages over other treatment options," stated Dr. J. Joseph Kim, President and Chief Executive Officer.

VGX will conduct Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) in its Phase I studies on VGX-1027. Upon successful completion, the results from these studies will satisfy FDA requirements to commence two Phase II studies: one for RA patients, to be conducted by VGX Pharmaceuticals, and one for T1D patients, to be conducted by its affiliate, VGX International.

VGX Pharmaceuticals

Intra-Articular Botulinum Toxin Type A May Offer Joint Pain Relief To Osteoarthritis Sufferers

2011-04-27T12:00:00.036-07:00

Injections of intra-articular neurotoxins may offer relief from severe knee pain for osteoarthritis patients who are not candidates for joint reconstruction, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Washington, DC.

For thousands of knee pain sufferers, arthroplasty is the solution of choice. This surgical replacement or reconstruction of the diseased joint restores function improves range of motion and decreases pain. However, for those who are too young, too old or too frail for such surgery, neurotoxins, which target the pain nerves within the joint, delivered to the knee joint cavity may provide sustained pain relief.

To determine the potential benefits of injecting a neurotoxin directly into the knee joint cavity, researchers embarked on a six-month study of Intra-articular Botulinum Toxin Type A (IA/BoNT/A) versus placebo in 37 patients with moderate to severe refractory knee pain due to osteoarthritis. IA/BoNT/A, otherwise known as Botox, disrupts pain nerve function and may reduce nerve-related inflammation.

The 36 men and one woman participating received either 100 units of IA/BoNT/A with lidocaine (a short-acting anesthetic) or a saline placebo with lidocaine. Double-blind assessments were scheduled for baseline, 1-month, 3-month and 6-month time points. Primary outcomes to be measured at each milestone include self-reported total pain score and a physical function score. A walking pain score, day pain severity, night pain severity and an observed timed-stands test were also measured.

At the 1-month interim analysis of this study, two placebo patients had dropped out from lack of benefit. Of the 18 patients in the severe pain group (half on IA/BoNT/A and half on placebo), there was a significant decrease in pain and improvement in physical function for those who received the botulinum toxin injection. Those injected with the placebo experienced minimal improvement. In the moderate pain group, neither injection produced significant changes in the primary outcome measures. Interestingly, in the moderate pain group, there was a 25% reduction in daytime pain severity after the placebo injections.

Three-month measurements will be completed by January of 2007, and the trial is scheduled for completion in August of 2007. To date, however, researchers point to clinically and statistically significant decreases in severe osteoarthritis knee pain and improvements in physical function.

"If this novel approach to local treatment for refractory join pain continues to prove beneficial, it offers a very welcome solution for fragile patients," explains Maren L. Mahowald, MD, Rheumatology Section Chief at the Minneapolis VA Medical Center, Professor of Medicine at the University of Minnesota, Minneapolis, Minnesota, and principal investigator in the study. "Local joint treatment with injection could replace oral medications that carry the risk of systemic side effects, and may negate or delay the need for joint surgery. Much more research will be needed to determine the most effective and safe dose of toxin for the joint injections and the most appropriate dosing intervals."

The American College of Rheumatology is the professional organization for rheumatologists and health professionals who share a dedication to healing, preventing disability and curing arthritis and related rheumatic and musculoskeletal diseases. For more information on the ACR's annual meeting, see rheumatology/annual.

Editor's Notes: Dr. Mahowald will present this research during a scientific poster session at the ACR Annual Scientific Meeting from 9:00 - 11:00 am EST on Monday, November 13, 2006 in Exhibit Hall A-B of The Washington Convention Center. She will be available for media questions and briefing at 8:30 am EST on Monday, November13, in the on-site Press Conference Room 209C.

Presentation Number: L1

Interim Report of a Randomized Double Blind Controlled Trial of Intra-articular Botulinum Toxin Type A (IA-BoNT/A) vs Placebo for Moderate and Severe Refractory Knee Pain due to Osteoarthritis

Mahowald L. Mahowald1, Jasvinder A. Singh1, Anton Kushnaryov2, Hollis E. Krug1. 1Minneapolis VA Medical Center & University of Minnesota, Minneapolis, MN; 2University of Minnesota, Minneapolis, MN

Moderate and Severe OA knee pain refractory to oral and IA treatment in patients too young or too old and frail for arthroplasty represents a growing unmet need for new joint pain treatments. IA Neurotoxin injection for sustained analgesia is a promising new approach to persistent joint pain (J Neurotox Res 9:179-88,2006). BoNT/A inhibits vesicle release of neuropeptides such as Substance P and CGRP and disrupts nociceptor function to decrease pain and neurogenic inflammation.

Purpose: To describe the effects of IA-BoNT/A injections at 1 month (interim analysis).

Methods: 37 patients with moderate to severe, refractory knee pain due to OA have been randomized to 100 units IA-BoNT/A+lidocaine (B) or saline+lidocaine placebo (P). Double blind assessments are made at baseline, 1 mo, 3 mo and 6 mo/time of withdrawal. Primary outcome measures at 1 mo were Western Ontario McMaster OA index (WOMAC) Pain Score & Function Score. WOMAC Q1-walking pain, Day Pain and Night Pain on 0 to 10 numerical rating scale (NRS) & 10X Timed Stands Test (TST) were also compared. Patients in the Severe Pain group had 7 or greater on NRS & the Moderate Pain group had 4.5 to

Enbrel Receives European Union Approval For Expanded Use In Rheumatoid Arthritis Patients

2011-04-27T12:00:00.035-07:00

Wyeth Pharmaceuticals, a division of Wyeth, today announced that the European Commission has approved ENBREL® (25 mg twice weekly), for use in combination with methotrexate for the treatment of active rheumatoid arthritis (RA) in adults when the response to disease-modifying antirheumatic drugs (DMARDs) (including methotrexate unless contraindicated) has been inadequate. This new indication is in addition to the previously approved indication for use of ENBREL as monotherapy in the treatment of active RA.

This approval is based on one-year results from the Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO). In the study, RA patients treated with a combination of ENBREL and methotrexate demonstrated an improvement in X-ray findings as measured by the modified Total Sharp Score (TSS), and 80 percent of the patients experienced no progression of joint damage. Additionally, 37 percent of RA patients treated with combination therapy achieved clinical remission as measured by Disease Activity Score (DAS) improvement, and 43 percent experienced a 70 percent improvement in RA symptoms as measured by American College of Rheumatology (ACR) response criteria.

In the TEMPO study, patients were assigned to one of three treatment groups: ENBREL (25 mg twice weekly), methotrexate (up to 20 mg once weekly), or ENBREL (25 mg twice weekly) plus methotrexate. Progression of joint damage was evaluated using the modified TSS, an X-ray measurement of changes in joint damage. Patients receiving combination treatment with ENBREL and methotrexate achieved a mean improvement of -0.54 in the modified TSS compared to baseline. Eighty percent of patients in the combination group showed "no progression," which was defined as a change in modified TSS

"The data we've seen from the TEMPO trial - using ENBREL either alone or in combination with methotrexate for the treatment of RA - is truly exciting, offering many patients the option for effective treatment and possibly preventing radiographic progression in RA," says Dr. Joseph Camardo, Senior Vice President, Global Medical Affairs, Wyeth Pharmaceuticals.

"ENBREL has a history of proven efficacy and tolerability in RA, and new information gathered through clinical trials such as TEMPO allows us to explore new treatment options to help improve the lives of RA patients," says Dr. Magnus Jaderberg, Vice President of Global Medical Affairs and European Medical Director of Wyeth Pharmaceuticals. "We will also see the clinical two-year results from the TEMPO study presented at the European League Against Rheumatism (EULAR) congress in June, which will provide even more information that can help physicians make important treatment decisions for their RA patients."

ABOUT THE TEMPO STUDY

The TEMPO study randomized 682 patients with RA. Patients in the ENBREL TEMPO trial had active RA and had had an inadequate response to at least one DMARD other than methotrexate. In the study, treatment with ENBREL or combination therapy was generally well tolerated. No changes to the safety profile were observed, and the combination did not result in increased infections. No cases of tuberculosis or opportunistic infections were observed.

ABOUT RA

RA can be a painful and debilitating disease, and currently there is no known cure. RA can cause stiffness, swelling, and limitation in the motion and function of multiple joints. If RA is not aggressively treated or is left untreated, patients can become disabled from joint damage caused by the disease, limiting their ability to function.

ABOUT ENBREL

Wyeth Pharmaceuticals markets ENBREL outside North America. ENBREL was discovered by Immunex, now part of Amgen (NASDAQ: AMGN), and jointly developed with Wyeth Pharmaceuticals. The two companies co-promote ENBREL in North America.

In the European Union, ENBREL is approved alone or in combination with methotrexate for the treatment of active rheumatoid arthritis in adults when the response to disease-modifying antirheumatic drugs, including methotrextate (unless contraindicated), has been inadequate. ENBREL is also indicated in the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate. In patients with rheumatoid arthritis, ENBREL used alone or in combination with methotrexate has been shown to slow the progression of disease-associated structural damage as measured by X-ray. ENBREL is also approved for the treatment of active polyarticular-course juvenile chronic arthritis in children aged 4 to 17 years who have had an inadequate response to, or who have proved intolerant of, methotrexate. ENBREL is also approved for the treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying antirheumatic drug therapy has been inadequate and for the treatment of adults with severe active ankylosing spondylitis who have had an inadequate response to conventional therapy.

Rheumatologists have become familiar with the benefits and long-term tolerability profile of ENBREL since it became commercially available nearly five years ago. More than 234,000 patients have been treated worldwide across indications. ENBREL (etanercept) acts by binding tumor necrosis factor (TNF), one of the dominant inflammatory cytokines or regulatory proteins that play an important role in both normal immune function and the cascade of reactions that causes the inflammatory process of psoriatic arthritis and RA. The binding of ENBREL to TNF renders the bound TNF biologically inactive, which can result in significant reduction in inflammatory activity.

Since the product was first introduced, serious infections, some involving death, have been reported in patients using ENBREL. Patients should tell their doctor if they currently have an infection or are prone to getting infections. Patients should not start ENBREL if they have an infection of any type or an allergy to ENBREL or its components. ENBREL should be used with caution in patients prone to infection.

There have been reports of serious nervous-system disorders such as multiple sclerosis and/or inflammation of the nerves of the eyes. Patients should inform their doctor if they have ever had any of these disorders or if they develop them after starting ENBREL. Patients should also tell their doctor if they have ever been treated for heart failure. There also have been rare reports of serious blood disorders, some involving death.

Patients should contact their doctor immediately if they develop symptoms such as persistent fever, bruising, bleeding, or paleness. It is unclear if ENBREL has caused these nervous-system or blood disorders. If a patient's doctor confirms serious blood problems, patients may need to stop using ENBREL.

The most frequent adverse events in clinical trials were injection-site reactions (ISRs) (36%), infections (35%), and headache (17%). Malignancies were rare. Only the rate of ISRs was higher than that of placebo. Adverse events in the psoriatic arthritis trial were similar to those reported in RA clinical trials.

ABOUT WYETH

Wyeth Pharmaceuticals, a division of Wyeth, has leading products in the areas of women's health care, cardiovascular disease, central nervous system, inflammation, hemophilia, oncology and vaccines. Wyeth is one of the world's largest research-driven pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing, and marketing of pharmaceuticals, vaccines, biotechnology products and non-prescription medicines that improve the quality of life for people worldwide. The Company's major divisions include Wyeth Pharmaceuticals, Wyeth Consumer Healthcare and Fort Dodge Animal Health.

Media

Jenifer Antonacci

Wyeth Pharmaceuticals

484-865-5220

wyeth

View drug information on Enbrel.

Patients With Chronic Rhinosinusitis Have Increased Incidence Of Other Chronic Illnesses

2011-04-27T12:00:00.034-07:00

Patients who suffer from chronic rhinosinusitis (CRS) also tend to suffer from other chronic illnesses, like asthma, hypertension, and arthritis.

In a paper presented at the 2009 American Academy of Otolaryngology - Head and Neck Surgery Foundation (AAO-HNSF) Annual Meeting & OTO EXPO in San Diego, researchers studied the electronic records of 1,970,695 patients to determine whether there was a relationship between CRS and other chronic conditions. Chronic rhinosinusitis is an inflammatory condition involving one or more of the paranasal sinuses. The condition usually follows an allergic reaction or viral upper respiratory infection.

The analysis showed a higher incidence of CRS in patients with other chronic diseases, especially asthma patients, who are more likely to also have nasal polyps. Patients with other chronic diseases such as high blood pressure and arthritis also have higher incidence of chronic sinusitis but not nasal polyps.

The results of the study suggest that some of these chronic diseases may share common mechanisms of how they arise or progress.

Title: CRS in the setting of other chronic illnesses

Presenters: Rakesh Chandra, MD; David Conley, MD; Robert Kern, MD; Robert Schleimer, PhD; Sana Sweis, MD; David Lin

Source:
Jessica Mikulski

American Academy of Otolaryngology -- Head and Neck Surgery

Safety In The Kitchen For Rheumatoid Arthritis Sufferers

2011-04-27T12:00:00.033-07:00

For sufferers of rheumatoid arthritis (RA), cooking tasks can be both difficult and dangerous. However, a new assistive technology invented by a Queensland University of Technology (QUT) student offers a safe way for people to lift cookware, relying on the strength of their forearms.

His design has earned a spot on the first-round shortlist of one of the world's most prestigious design competitions - the Australian Design Award/James Dyson Award.

Twenty-four-year-old Ching-Hao (Howard) Hsu, who graduated with a Bachelor of Design (Industrial Design) at the end of 2010, designed the 'arthritis handle' after observing several sufferers of rheumatoid arthritis performing cooking tasks in their own kitchens.

RA is a chronic disease affecting one percent of the population - about 500,000 Australians. It involves inflammation of the joints, which can lead to stiffness, swelling and sometimes disablement in the hands.

"After several observations and lots of interviews, I found that lifting was a major problem for sufferers of RA during cooking preparation," Mr Hsu said.

"It was difficult for sufferers of RA to lift things with their hands, due to having limited strength and flexibility. So they had to lift with their forearms. This limited them to using cookware with handles on both sides.

"If a saucepan only had one handle, most people put a towel over their other forearm to grasp the opposite side of the pot, but this was a slippery and dangerous way of lifting, exposing the person to the risk of burns.

"The arthritis handle allows sufferers of RA to use any kind of cookware, and not be limited to double-handled products.

"Due to the limited flexibility of a hand with RA, the ergonomically-designed finger holder at the front of the arthritis handle fits comfortably on the user's hand without twisting the user's fingers.

"The shape of the arthritis handle is also ergonomic, in that it spreads the weight of the cookware across the user's forearm."

Mr Hsu said the arthritis handle featured a silicone coating with heat resistance up to 200 degrees celsius, to prevent heat from being directed to the forearm.

"The TPE (thermoplastic elastomers) used in the product provide grip, while a magnetic strip enhances the stability for people lifting metal cookware," he said.

"I want to make sure that the arthritis handle is eventually made available in various colours. People using assistive technologies often hate sticking out as being a 'special' person. So I want this to look like a normal kitchen tool, with the inner frame available in bright orange, yellow or green, with a white outer frame."

Notes:

Mr Hsu, who grew up in Taiwan, began his masters in lighting engineering at QUT in February, and hopes to work on environmentally friendly products in the future.

The arthritis handle has also been entered in the Kitchen Tools International Design Competition.

Source:

Michaela Ryan

Queensland University of Technology

Targeting Disease Remission Has Socio-Economic Benefits Over Low Disease Activity

2011-04-27T12:00:00.032-07:00

Achieving disease remission in patients with rheumatoid arthritis (RA) provides superior outcomes across measures of socio-economic importance including work productivity and quality of life, according to results presented at EULAR 2010, the Annual Congress of the European League Against Rheumatism in Rome, Italy. These Austrian findings are reported in addition to improvements in measures of physical functioning, when compared with RA patients achieving low disease activity (LDA).

Results from this cross-sectional study of 356 patients showed statistically significant differences (p= < 0.01) between RA patients who had achieved disease remission (REM, defined by the Clinical disease activity Index (CDAI), a composite index including objective and patient derived scores) compared to those who had achieved LDA across several domains including:
Effect on work productivity, based on results of the Work Productivity and Activity Impairment (WPAI*) index: impairment while working 11.3% vs. 27.2%, overall activity impairment 18.1% vs. 33.8%, REM vs LDA respectively
Impact on quality of life, based on results of the Euro Qol (5D EQ-5D)* index: 0.89 vs. 0.78 and the SF-36 PCS* index: 46.2 vs. 37.8
Impact on physical functioning, based on results of the Health Assessment Questionnaire (HAQ*) scores: 0.38 vs. 0.75.

"We know that RA as a chronic disease often has a long term impact on patients' functional ability, affecting not only patients' well-being but also their working lives. The majority of those affected report a loss of productivity at work, and many even have to stop work altogether," said Dr. Helga Radner, Department of Rheumatology, Medical University Vienna, Austria and lead author of the study. "Our study results show that the benefits of achieving clinical remission are worthwhile, especially from a socio-economic point of view, as it decreases the 'burden of disease' not only for patients but also for society on a wider scale. The findings reveal that remission is even superior to an almost perfect disease activity state, namely low disease activity, therefore our major task in treating RA-patients should be its achievement and maintenance"

Interestingly, researchers found that the emotional aspects of the disease activity measures were similarly reported in patients in remission and in low disease activity indicating that once disease activity or symptom levels are reduced to a certain level, emotional discord may stabilise.

Longitudinal analysis over one year showed significant improvements when comparing the two patient populations in the following areas:
Quality of life (EQ-5D); 0.89 vs. 0.80 (REM vs. LDA respectively), p < 0.001
Percent of overall activity impairment (WPAI) per year; 12.2% vs. 31.0%, p < 0.001
Physical disability (HAQ); 0.23 vs. 0.69, p= < 0.001

Significant differences between REM and LDA were not seen in the domain of percentage impairment while working (8.3% vs. 20.0% (REM vs. LDA respectively), p=0.096).

This study of 356 patients registered at the Department of Rheumatology at the Medical University of Vienna involved one cross sectional analysis (at a single time point) of RA patients, with 34 patients achieving REM (CDAI ?‰¤2.8) and 66 patients achieving LDA (2.8?‰¤CDAI

Sea Snail Key To Future Of Pain Relief

2011-04-27T12:00:00.031-07:00

Unique research at The University of Queensland could revolutionise the treatment of pain relief - thanks to a humble sea snail.

Dr Jenny Ekberg, a Research Fellow with UQ's School of Biomedical Sciences, has studied a toxin produced by a marine snail found on the Great Barrier Reef, which has the ability to precisely target chronic pain without severe side-effects.

"Chronic pain can be caused by an initial injury that affects the nerves, or conditions such as diabetes and arthritis," Dr Ekberg said.

"The problem with current drugs, such as morphine, is that they sometimes offer only marginal relief and come coupled with lots of problems with tolerance and side-effects.

"Our research show that a natural product, a conotoxin from the marine snail Conus marmoreus, produces pain relief without apparent side-effects in animal models of chronic pain."

The study, done with colleagues Professor David Adams in the School of Biomedical Sciences, Dr Richard Lewis at UQ's Institute for Molecular Bioscience and Professor Mac Christie at the University of Sydney, was recently published in the Proceedings of the National Academy of Sciences.

Dr Ekberg said with approximately one in five Australians will suffer from chronic pain at some point in their life the potential benefit of this research could be enormous.

She said sufferers of chronic pain can have the added problem of being diagnosed with no reason for the pain.

"The patient experiences severe pain because their nerve cells that are responsible for pain transmission are overactive," she said.

"This is primarily due to abnormal activity of voltage-gated sodium channels in the nerve cells.

"Conventional drugs, such as local anaesthetics, block all types of sodium channels, causing severe side-effects.

"Our toxin only blocks a specific channel - the first time a toxin like this has been shown to work - therefore providing pain relief without severe side-effects."

Dr Ekberg said it would be a number of years before such a treatment would be commercially available.

Originally from Sweden, Dr Ekberg came to UQ to complete her Honours in Biomedical Sciences and stayed to complete a PhD, from which this research stemmed, under the supervision of Professor David Adams and Associate Professor Phil Poronnik.

Dr Ekberg said she has since remained at UQ because of a combination of high-class research and a wonderful environment.

For further information please go to:
The University of Queensland, Brisbane Australia
Source:
UQ News Online

A Recommendation For Early And Aggressive Arthritis Treatment - Results From 11-Year Trial

2011-04-27T12:00:00.030-07:00

Disease-modifying antirheumatic drugs (DMARDs) should be used early and aggressively at the first sign of rheumatoid arthritis (RA). The results of an 11-year trial, published in BioMed Central's open access journal Arthritis Research & Therapy, demonstrate that active treatment from the very beginning pays off, even in the long run.

Dr Vappu Rantalaiho, from Tampere University Hospital, Finland, worked with a team of researchers to study radiologic progression in 195 patients with RA. She said, "Early therapy with combinations of conventional DMARDs has been shown to retard the radiologic progression of RA for a period of up to 5 years, but until now the effects of initial aggressive DMARD therapy on radiologic prognosis after that were unknown. We've shown that even after 11 years, early and aggressive therapy achieves excellent results for most patients".

For this study, 97 patients were initially randomized to receive a combination of DMARDs (starting with methotrexate, sulfasalazine, and hydroxychloroquine with prednisolone; FIN-RACo strategy) and 98 received a single DMARD (initially sulfasalazine with or without prednisolone; SINGLE strategy). After 2 years, the treatment of RA was unrestricted for both groups. Patients treated initially with the FIN-RACo strategy were found to have less radiographic damage in small joints, even in the long term, than those treated initially with DMARD monotherapy. According to Rantalaiho, "Probably the most important precondition to our excellent results in most patients was the active treatment policy aiming at remission at all time points. Our results emphasize the importance of early remission for long term outcome. In the present study, the patients who were in strict remission at 1 year had significantly less radiologic progression throughout the follow-up than the patients who were not".

Notes:

Early combination disease-modifying antirheumatic drug therapy and tight disease control improve long-term radiologic outcome in patients with early rheumatoid arthritis: the 11-year results of the Finnish Rheumatoid Arthritis Combination Therapy trial

Vappu Rantalaiho, Markku Korpela, Leena Laasonen, Hannu Kautiainen, Salme Jarvenpaa, Pekka Hannonen, Marjatta Leirisalo-Repo, Harri Blafield, Kari Puolakka, Anna Karjalainen, Timo Mottonen and the FIN-RACo Trial Group

Arthritis Research & Therapy (in press)

Source: BioMed Central

FDA Advisory Committee Recommends Approval Of Celebrex For Use In Children

2011-04-27T12:00:00.029-07:00

An FDA advisory panel on Wednesday voted 15-1 to recommend approval of Pfizer's pain medication Celebrex for the treatment of rheumatoid arthritis in children, even though some panel members questioned the long-term safety of the drug, the Wall Street Journal reports (Kowsmann, Wall Street Journal, 11/30). On Tuesday, FDA said Pfizer might have to conduct additional studies of Celebrex before it could be approved for use in children. The drug, which is approved to treat arthritis in adults, is the only member of a class of medications called COX-2 inhibitors, which include Vioxx and Bextra, not to have been withdrawn from the market over concerns of increased risk for heart attacks and stroke. Pfizer this year requested FDA approval for Celebrex as a treatment for rheumatoid arthritis in children ages two and older. According to FDA, about 30,000 to 60,000 children in the U.S. have rheumatoid arthritis. Drugs approved to treat the condition include aspirin, ibuprofen and naproxen. The heart attack risk for children who take the drug is unknown (Kowsmann, Wall Street Journal, 11/29).

Panel Recommendation
The panel said it decided to recommend approval of the drug because new treatments are needed for juvenile rheumatoid arthritis and Celebrex has been shown to be an effective treatment (Wall Street Journal, 11/30). The panel recommended that Pfizer establish a patient registry to track for up to three decades health indicators like blood pressure and kidney function in children who take Celebrex. Panel members said the drug potentially places children at a higher risk of having a heart attack later in life (Henderson, Boston Globe, 11/30). Panel member Joan Bathon, a rheumatologist at Johns Hopkins University, said, "The [panel's] feeling was short-term efficacy looked good and short-term safety was not an issue. Long-term safety is totally unknown and needs to be known." Steven Romano, a vice president in Pfizer's worldwide medical division, said, "That's not unreasonable. But the important part, when they considered both safety and benefit, is the benefits outweighed the risks" (Bridges, AP/Newark Star-Ledger, 11/30). Panel member Eric Holmboe, vice president of the American Board of Internal Medicine, criticized Pfizer's proposal to monitor the drug's side effects through reports physicians file with FDA. He said a voluntary reporting system would be a "very weak instrument" for tracking long-term health effects of the drug (Boston Globe, 11/30).

"Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

View drug information on Bextra; Vioxx.

Deterioration In Mental Health Associated With Worse Pain In Osteoarthritis

2011-04-27T12:00:00.028-07:00

How much pain osteoarthritis sufferers feel is directly related to their mental health, a new study by researchers at UC Davis School of Medicine has found. In the study, people with better mental health felt less pain, and people with worse mental health felt more.

The study suggests that mental-health treatment could be an effective way to lessen arthritis pain.

"We found that increased levels of pain were associated with worse mental health at baseline," said Barton L. Wise, an assistant professor of general internal medicine and the study's lead author. "And further, pain flares were associated with poorer mental health during the week prior to the pain flare."

The study, "Psychological Factors and Their Relation to Osteoarthritis Pain," is published in the journal Osteoarthritis and Cartilage. Wise, who is a researcher with the UC Davis Center for Healthy Aging, said he and his colleagues conducted the research because of the episodic nature of osteoarthritic pain. How much pain a person feels in their arthritic knee or hip may change, and those changes may not be related to structural changes in their joints.

"Pain varies over time, both over extended periods and over shorter periods," Wise said. "The same person can feel little or no pain in their knee or hip, and later they can feel moderate-to-severe pain even when the extent of damage to the knee or hip joint as seen on x-ray imaging remains the same."

Osteoarthritis is a degenerative disease involving the loss of cartilage and bone at the joints. Typical symptoms include joint pain, tenderness and stiffness, usually in the knees, hips and spine. It is the most common form of arthritis, and also is known as degenerative joint disease. Osteoarthritis has an estimated 27 million sufferers in the United States and is a leading cause of knee- and hip-replacement surgery, according to the Centers for Disease Control and Prevention.

The researchers studied 266 subjects in the Longitudinal Examination of Arthritis Pain Study, which investigated the relationship between pain, fluctuations in pain and health outcomes. During telephone interviews, the participants, all of whom had hip or knee pain, responded to questions about their pain and psychological states. The interviews took place at one-week intervals over a 12-week period. Mental health was scored using the Mental Health Index-5, with high scores indicating better mental health on a scale of five to 30. Pain was scored using the Western Ontario and McMaster University Osteoarthritis Index of 0 to 10, with a score of 10 indicating severe pain.

Better baseline mental health, a mental-health index score of 28 to 30, was associated with less pain and a relatively low score of 2.93 on the osteoarthritis pain index scale. Participants with worse mental health had mental-health index scores of 13 to 22 and a relatively high osteoarthritis pain index score of 4.57. In addition, patients with worse mental health - mental-health index scores in the 13-to-22 range - had double the risk of increased pain flares as compared with participants in the 28-to-30 range.

Wise said that part of the study's strength is that it gauged individuals' perceptions of their pain intensity at different times, as well as comparing different participants' pain experiences.

"Pain is difficult to study in part because experiences and reporting of pain differ from one person to another. There can be differences in people's central or peripheral nervous systems, past experiences of pain or cultural differences in perceptions of pain, and these make it very complicated to look at differences in pain across individuals. Our study design helped eliminate some of those obstacles," he said. "But it's likely that people's pain is the result of a large group of different factors rather than something as simple as one specific physiological factor."

While the study did not measure whether participants suffered from clinical conditions like depression, it suggests that mental-health treatment could improve patients' osteoarthritis pain - especially because there are no medications that have been proven effective for changing the overall course of osteoarthritis. Current treatments for osteoarthritis include weight loss, improved diet, vitamin consumption and over-the-counter analgesics like acetaminophen or ibuprofen.

"With the paucity of effective interventions for osteoarthritis pain and the toxicities of some in common use, mental health may represent a new therapeutic target for osteoarthritic pain, with potential significant opportunities for both patients and physicians," the study says.

Wise conducted the study while in the Clinical Epidemiology Research and Training Unit at Boston University School of Medicine as well as while at UC Davis. Other study authors include J. Niu and Y. Zhang, both of Boston University; J.M. Jordan of the University of North Carolina Medical Center; E. Choy of the Academic Department of Rheumatology, King's College, London; and D.J. Hunter of the Division of Research, New England Baptist Hospital.

The study was supported by the UC Davis School of Medicine Building Interdisciplinary Research Careers in Women's Health Program.

Source:

Phyllis Brown

University of California - Davis - Health System

Investigating the role of T cells in rheumatoid arthritis

2011-04-27T12:00:00.027-07:00

Rheumatoid arthritis is a chronic inflammatory disease leading to joint destruction. Considered by some to be an
autoimmune disorder where immune complexes are formed in the joints and excite an inflammatory response, various genetic,
environmental, and infectious agents have been suggested as causes of the disease. IL-1 is a proinflammatory molecule
produced by cells of the immune system and cells lining the joints and it has been suggested that IL-1 may have a role in the
development of RA.

The body also produces a natural inhibitor to IL-1, IL-1 receptor antagonist (IL-1Ra), the levels
of which are augmented in patients with autoimmune and inflammatory diseases. Another proinflammatory agent, TNF-a,
stimulates IL-1 expression and vice versa.

In the December 1 issue of the Journal of Clinical Investigation, Yoichiro Iwakura and colleagues from the University of
Tokyo studied the role of T cells in the development of autoimmune arthritis in mice lacking IL-1Ra.

The authors demonstrated that mice deficient in both T cells and IL-1Ra did not develop arthritis. Arthritis development also
appeared to be markedly decreased in cases of TNF-alpha deficiency.

The authors found that IL-1Ra produced by these T cells act on the T cells themselves to induce TNF-alpha expression and
TNF-alpha in turn induces OX40 expression on T cells. As inhibition of TNF-a or OX40, the latter being an activation antigen
on T cells, which invade tissues and cause autoimmune destruction - was effective in suppressing the development of
arthritis, the authors suggest that their study may provide a clue for the development of new therapies for RA.

TITLE: TNF-alpha is crucial for the development of autoimmune arthritis in IL-1 receptor antagonist-deficient mice

AUTHOR CONTACT:

Yoichiro Iwakura

Center for Experimental Medicine

University of Tokyo

Tokyo, Japan

Contact: Brooke Grindlinger

press_releasesthe-jci

212-342-0497

Journal of Clinical Investigation

Genetic Link Found Between Spinal Arthritis And Inflammatory Bowel Disease

2011-04-27T12:00:00.026-07:00

Researchers at the University of Queensland Diamantina Institute in Brisbane, Australia, have found that a form of spinal arthritis is genetically linked to Inflammatory Bowel Disease. The study will be published on December 2 in the open-access journal PLoS Genetics.

Ankylosing Spondylitis (AS) is a common form of arthritis involving chronic inflammation particularly of the spinal and pelvic joints, which causes pain, stiffness, and often disability. Affecting up to 0.5% of the population, the risk of AS is almost entirely genetically determined. Curiously, AS patients appear to be highly susceptible to Inflammatory Bowel Disease (IBD), including Crohn's disease. Similarly, the development of AS is common in IBD patients. Professor Matt Brown and his colleagues wanted to determine if this was more than a coincidence.

"It seemed likely that common pathogenic pathways may be acting in the development of both diseases" said Professor Brown.

In order to test whether genes associated with Crohn's disease are also associated with AS, they searched for known genetic markers of Crohn's disease in the genomes of more than 2700 AS patients, working with colleagues from England, North America and Canada. The results revealed that both AS and Crohn's disease share several similar genetic variations, and identified seven genes affecting both conditions.

When the researchers took a closer look at the function of the genes they had identified, they found that four of the genes are known to influence the activation of a recently discovered class of helper T-cells called Th17 cells. Identifying the involvement of these immune cells greatly increases what is known about how AS develops, and points to potential new therapies for this form of arthritis. This study highlights the value of studies that look into individual genes that might be implicated in related diseases.

Financial Disclosure: This study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) grants P01-052915 and R01-AR046208. Funding was also received from the University of Texas at Houston CTSA grant UL1RR024188, Cedars-Sinai GCRC grant MO1-RR00425, Intramural Research Program, NIAMS/NIH, and Rebecca Cooper Foundation (Australia). MAB is funded by the National Health and Medical Research Council (Australia). Support was also received from the National Institute for Health Research (UK) Oxford Biomedical Research Centre ankylosing spondylitis chronic disease cohort (Theme Code A91202), NIHR Oxford Musculoskeletal Biomedical Research Unit and the NIHR Thames Valley Collaborative Local Research Network, and Princess Alexandra Hospital Research Foundation. We would like to thank the National Ankylosing Spondylitis Society (UK) for assistance in patient recruitment and the Arthritis Research Campaign (UK) for financial support under grants 19356 and 18797. The Spondyloarthritis Research Consortium of Canada (SPARCC) is supported by a National Research Initiative (NRI) award from the Arthritis Society of Canada. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

Citation: Danoy P, Pryce K, Hadler J, Bradbury LA, Farrar C, et al. (2010) Association of Variants at 1q32 and STAT3 with Ankylosing Spondylitis Suggests Genetic Overlap with Crohn's Disease. PLoS Genet 6(12): e1001195.
doi:10.1371/journal.pgen.1001195

Source:

PLoS Genetics

Role Of Bone Hardness In Tissue Function Revealed By Hearing Loss Study

2011-04-27T12:00:00.025-07:00

Scientists are reporting the first direct evidence that a subtle change in the physical properties of a tissue can affect its function. The finding has immediate implications for understanding several rare hearing disorders, they said, and ultimately could offer insight into such conditions as osteoporosis, arthritis, cardiovascular disease and cancer.

In their study, the scientists discovered that blocking the function of a particular molecule in the ear bone of mice decreased the hardness of the bone, causing hearing loss. Reactivating the molecule restored the bone's hardness - and the animals' hearing.

The research likely explains the previously unknown cause of hearing loss in the human disease cleidocranial dysplasia, a genetic bone syndrome,said co-author Lawrence Lustig, MD, UCSF professor of otolaryngology, and may explain hearing loss associated with some other bone diseases.

More broadly, the finding reveals the molecular pathway that regulates the physical properties of extracellular matrix - the interlocking mesh of molecules between cells - in the ear's cochlear bone. The matrix is responsible for the hardness of human tissues, ranging from stiff bone and enamel to compliant brain and skin.

Perhaps most intriguing is the discovery that variations in the physical properties of extracellular matrix affect tissue function. This finding should lead to insights into abnormal matrix properties in the tissues of diseases throughout the body, the researchers said, including osteoporosis and arthritis.

"Our finding demonstrates that establishing and maintaining the proper calibration of physical properties is essential for healthy tissue function," said the senior author of the study, Tamara Alliston, PhD, assistant professor of orthopaedic surgery and a member of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.

Scientists have known that physical cues, such as extracellular matrix stiffness, direct the differentiation of stem cells into specific cell types, such as heart, liver and brain cells. They also have known that disruption of these cues underlies a wide range of diseases, such as osteoarthritis, cardiovascular disease and cancer.

However, they have not known the molecular mechanisms that establish the physical properties of extracellular matrix, nor the link between these properties and tissue function.

In the current study, recently reported in EMBO, the team, led by Jolie L. Chang, MD, a resident in the UCSF Department of Otolaryngology and Head and Neck Surgery, set out to investigate the mechanisms involved.

Earlier studies, conducted at UCSF, showed that a molecule known as transforming growth factor beta (TGF-??) regulates the turnover of bone cells known as osteoblasts, by inhibiting a molecule known as Runx2. Disrupting TGF-??'s regulation of Runx2 causes dysplastic clavicles and open cranial sutures.

These skeletal deformities, seen in the human genetic bone disease cleidocranial dysplasia, result from a defective copy of the Runx2 gene. Patients with CCD experience "sensorineural" hearing loss - caused by damage to the cochlear bone or nerve damage.

Given these conditions, the teams used two mouse models of CCD to study the regulation and role of bone matrix properties in the cochlear bone.

They focused on this bone in part because of anecdotal evidence in patients, and research in whales, flamingos and polar bears, indicating that the bone is the hardest in the body, in the case of whales possibly helping the animals hear under water. The required stiffness, the team suspected, likely would be precisely calibrated.

They first conducted a nanoscale analysis of several mouse bones in the head and ear, establishing that the cochlea bone was by far the stiffest.

Then, in what they considered a major insight, they discovered that TGF-?? regulates Runx2 to establish the physical property of the extracellular matrix of the cochlea bone. "This told us," said Chang, "that Runx2 - a key transcriptional regulator that helps the cell select its cell fate - also controls the physical properties of the matrix."

Finally, by manipulating Runx2 activity through TGF-??, the team determined that the physical quality of the bone matrix affects hearing.

Now, the team is investigating the molecules "downstream" of Runx2, to gain further insight into the mechanism regulating the physical properties of bone. They also are studying if these mechanisms define the stiffness of matrices in other skeletal tissues.

"We want to see if TGF-?? targets the cartilage transcription factor to make cartilage more or less stiff," Alliston said. "We think that the stiffness is degraded in arthritis and that this further disrupts chondrocyte cells, exacerbating the disease."

Notes:

Other co-authors of the study are Delia S. Brauer, Jacob Johnson, Carol Chen, Omar Akil, Emily N. Chin, Kristen Butcher, Richard A. Schneider, Anil Lalwani, Rik Derynck, Grayson W. Marshall, and Sally J. Marshall, of UCSF, Guive Balooch, at the time a postdoctoral fellow in the lab of co-author Robert O. Ritchie, of UC Lawrence Berkeley National Laboratories, Mary Beth Humphrey, of University of Oklahoma Health Science Center, and Alexandra E Porter, of Imperial College London.

The study was funded primarily by the National Institutes of Health, the Deafness Research Foundation, The Arthritis Foundation, UCSF School of Dentistry Creativity Fund, Arthritis Foundation, Deafness Research Foundation and Department of Energy.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

Source:

Jennifer O'Brien

University of California - San Francisco

Searching For The Best Biologics For Rheumatoid Arthritis

2011-04-27T12:00:00.024-07:00

More studies that directly compare the effectiveness of different biologic drugs for rheumatoid arthritis (RA) are needed, say Cochrane Researchers. The researchers reviewed all previous Cochrane Systematic Reviews assessing the effectiveness of biologic disease-modifying drugs for treatment of RA and found that although all were very effective, there was little data on direct comparisons between the drugs that could help doctors decide which to prescribe.

RA is an autoimmune disease that affects up to 1 in 100 people in Western countries. Patients experience chronic pain and inflammation as a result of the body's own immune system attacking the lining of the joints. In recent years, biologic disease-modifying anti-rheumatic drugs (DMARDs) have been introduced that can help to modify this irregular immune response and improve symptoms of the disease. Although these drugs may have fewer side effects than traditional DMARDs such as methotrexate, they are more expensive.

The six previous reviews considered by the researchers used two measures to make indirect comparisons between different biologic drugs. The first was doctor or patient assessment of symptoms including the number of swollen joints. For adalimumab, etanercept and rituximab, an increase of at least 40% was seen in the number of people experiencing improved symptoms, when the drugs were compared to placebos. Anakinra was the least effective at just 6% improvement compared to placebos. The second measure was the number of people who dropped out of studies due to adverse effects. Less than 10% dropped out in most cases, however, etanercept, abatacept and infliximab seemed to be responsible for the fewest withdrawals, showing little difference to the numbers dropping out when taking placebos.

"Doctors are faced with a difficult dilemma when choosing biologics to prescribe to RA patients. Although anakinra seemed less effective in the trials we looked at, we did not have any data from direct comparisons between different drugs," says lead researcher Jasvinder Singh, who is based at the Minneapolis Veterans Affairs Medical Center in Minneapolis in the US.

"We believe that direct head-to-head comparisons of biologic drugs in patients suffering from RA are needed. These trials should examine efficacy and safety at different stages and severity levels of the disease, as well as prior treatment with other drugs."

Source:
Jennifer Beal

Wiley-Blackwell

Rheumatoid Arthritis Patients Receiving Anti-TNF Therapy Can Be Effectively Immunized

2011-04-27T12:00:00.023-07:00

Despite being immunosuppressed, patients with rheumatoid arthritis are able to develop protective antibodies following pneumococcal and influenza vaccinations when also treated with anti-TNF agents, thus reducing their risk for developing the flu and the most common type of bacterial pneumonia, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Washington, DC.

Flu shots are given annually to combat the influenza that plagues 5 to 20 percent of Americans each year. In many cases, these infections can lead to severe complications, especially in the elderly and patients with chronic illnesses, causing approximately 36,000 annual deaths among Americans. Because patients with rheumatoid arthritis are immunosuppressed, there is longstanding concern about the effectiveness of vaccinations for disease prevention.

To examine the effectiveness of anti-bacterial pneumococcal vaccination and anti-viral influenza vaccinations, 226 patients with active rheumatoid arthritis participated in a double-blind study during the 2003-2004 influenza season. Each patient received either the biologic, adalimumab, or a placebo over a 30-day period. Those taking the biologic drug were given 80 mg on day 1 followed by 40 mg on days 15 and 29. Vaccines for pneumococcus (23-valent) and influenza virus (trivalent subvirion) were administrated intramuscularly to all patients on day 8. Response to vaccination was determined 4 weeks following vaccination (day 36).

Researchers found no significant difference between the adalimumab and placebo groups among the 208 patients with analyzable data when comparing the percentages of patients with protective antibody concentrations in response to both vaccines. This indicates that adalimumab therapy did not diminish the participants' abilities to develop the necessary protective immune response. Preliminary studies of several other biologic agents in rheumatoid arthritis suggest similar results, but this is the largest placebo-controlled study conducted to date.

"As physicians, we believe all patients at risk of influenza or pneumococcal pneumonia should receive vaccination regardless of whether or not they have rheumatoid arthritis," says Jeffrey Kaine, MD, Director, Sarasota Arthritis Research Center, Sarasota, Florida, and an investigator in the study. "However, the fact that we now have evidence to suggest that these vaccines are effective in the rheumatoid arthritis patient population offers physicians and their patients peace of mind."

The American College of Rheumatology is the professional organization for rheumatologists and health professionals who share a dedication to healing, preventing disability and curing arthritis and related rheumatic and musculoskeletal diseases. For more information on the ACR's annual meeting, see rheumatology/annual.

Presentation Number: 1235

Abilities to Develop Protective Antibodies to Pneumococcal and Influenza Vaccine are Maintained in Rheumatoid Arthritis (RA) Patients Treated with Adalimumab (Humira®)

J. Kaine1, A. Kivitz2, C. Birbara3, A. Y. Luo4. 1Sarasota Arthritis Center, Sarasota, FL; 2Altoona Center for Clinical Research, Duncansville, PA; 3Clinical Pharmacology Study Group, Worcester, MA; 4Abbott, Parsippany, NJ

Purpose: Streptococcus pneumoniae and influenza virus are prominent infectious agents that can cause morbidity and mortality in RA. Although routine pneumococcal and influenza vaccinations are recommended, treatment with steroids, immunosuppressants, and/or TNF antagonists may affect immune response. This study evaluated the effects of adalimumab on antibody (Ab) response to pneumococcal (pneum) and influenza (infz) vaccines in adult RA pts.

Methods: Patients (pts) with active RA were enrolled during the 2003-04 US infz season into this double-blind, placebo-controlled study. Pts randomized to adalimumab received 80 mg on Day 1 followed by 40 mg on Days 15 and 29. Standard 23-valent pneum and trivalent subviron infz virus vaccines were administered intramuscularly to all pts on Day 8. Ab titers (9V, 14, 18C, 19F, and 23F for pneum; H1N1, H3N2, and Hong Kong for infz) were measured on Day 8 (prevaccination) and Day 36. Protective Ab status for pneum vaccine was defined as ≥1.6 mg/mL in ≥3 of 5 antigens and response to vaccination was defined as ≥2-fold increase from baseline (BL) in Ab titer in ≥3 of 5 antigens. Protective Ab status for infz vaccine was defined as ≥1:40 titer in ≥2 of 3 antigens, and response to vaccination was defined as ≥4-fold increase from BL in Ab titer in ≥2 of 3 antigens.

Results: A total of 226 pts were randomized. The analysis comprised data from 208 pts who had received at least the first 2 doses of blinded study drug (on Days 1 and 15) and had both pre- and post-vaccine Ab analyses. No significant difference between groups existed in either BL demographics or Ab levels.

For pneum vaccine, the %s of pts with protective Ab status 4-weeks after vaccination were comparable in both arms, as were the %s of pts in both groups who developed Ab response. For infz vaccine, the %s of pts who had protective Ab status 4-weeks after vaccination were also comparable in the 2 groups. The % of pts who developed infz Ab response was smaller in the adalimumab arm, driven by the subgroup of pts that already had protective Ab status at BL. Among pts without protective Ab status at baseline, the response rates were similar in the 2 groups. The frequencies and types of adverse events were similar to those observed in other adalimumab studies.

4 Weeks After Vaccination Placebo Adalimumab

Influenza: protective antibody status 103/109 (94.5%) 97/99 (98.0%)
Influenza: developed antibody response 69/109 (63.3%) 51/99 (51.5%)
Response in patients with protective influenza antibody status at baseline 35/63 (55.6%) 21/58 (36.2%)

Response in patients without protective influenza antibody status at baseline 34/46 (73.9%) 30/41 (73.3%)

Pneumococcal: protective antibody Status 89/109 (81.7%) 85/99 (85.9%)
Pneumococcal: developed antibody response 44/109 (40.4%) 37/99 (37.4%)
Response in patients with protective pneumococcal antibody status at baseline 17/62 (27.4%) 16/57 (28.1%)

Response in patients without protective pneumococcal antibody status at baseline 27/47 (54.7%) 21//42 (50.0%)

Conclusion: Adalimumab does not diminish ability to develop protective antibody from pneumococcal and influenza vaccines in RA pts. These findings demonstrate that RA pts on adalimumab can be effectively and safely immunized with these vaccines.

Disclosure Block: J. Kaine, Abbott, 5 Consulting fees.

American College of Rheumatology (ACR)

1800 Century Place, Ste 250

Atlanta, GA 30345-4300

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View drug information on Humira.

Data Demonstrate ORENCIA(R) (abatacept) Improves Health-Related Quality Of Life, Pain And Sleep Quality In Children With Juvenile Idiopathic Arthritis

2011-04-27T12:00:00.022-07:00

Bristol-Myers Squibb Company (NYSE: BMY) today announced at the American College of Rheumatology (ACR) Annual Scientific Meeting in San Francisco results from a 10-month study which showed that ORENCIA® (abatacept), compared to placebo, significantly improved multiple aspects of health-related quality of life (HRQoL): physical and psychosocial well being, pain and sleep quality in juvenile idiopathic arthritis (JIA) patients between the ages 6 and 17 years. These improvements with ORENCIA were maintained throughout the 10-month study period, during which the first four months included an open-label lead-in period and the last six months comprised a randomized, double-blind, placebo-controlled study.

These results were part of a study looking at the safety and efficacy of ORENCIA in children with JIA who had failed on previous treatments such as methotrexate (MTX) or biologics.[1] Data from this study was used to obtain U.S. Food and Drug Administration approval of ORENCIA on April 8, 2008, for reducing the signs and symptoms in children and adolescents 6 years of age and older with moderate-to-severe polyarticular JIA. In children and adolescents, ORENCIA may be used alone or with MTX.[2]

"Health-related quality of life, or HRQoL, in children with JIA can be significantly impaired due to pain, joint damage and inflammation," said the study's lead investigator, Daniel Lovell, M.D., M.P.H., director, Division of Rheumatology, Cincinnati Children's Hospital Medical Center. "Therefore, successful treatment of JIA should positively impact patient-centered outcomes in HRQoL, daily functioning and psychosocial well being."

Study Design and Findings

In this 10-month, two-phase study, 190 children with JIA between the ages of 6 and 17 years were enrolled. In the first phase of the study (Period A), which was an open-label lead-in period, all patients were treated with ORENCIA 10 mg/kg intravenously at Day 1, 15, 29, and approximately every 28 days thereafter for four months. In Period B, patients who completed Period A and achieved an American College of Rheumatology Pediatric (ACR Pedi) 30 percent response-defined as 30 percent or more improvement in at least three of the six JIA core set variables and not more than one JIA core variable showing 30 percent or more worsening2-were then randomized to a double-blind withdrawal phase with ORENCIA® (abatacept) or placebo for up to six months (ORENCIA n=60; placebo n=62).

There were three validated measures in this study used to assess HRQoL. The first was the Child Health Questionnaire (CHQ), which contains 15 health domains covering a child's physical and psychosocial well being and the impact of JIA on parents and family.[3],[4] The second was sleep quality, as measured by the Children's Sleep Habits Questionnaire (CSHQ), which has eight domains that measure the most common sleep problems in children and adolescents: bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night walkings, parasomnias, sleep disordered breathing and daytime sleepiness.[5] The third measure was pain, assessed by a Visual Analog Scale (VAS) Score of 0 to 100 mm.[6] The VAS Score for pain is a global quality-of-life indicator in which the patient identifies along a continuum the amount of pain they are feeling.6 For these measures, mean change from baseline in each period was calculated and compared between the treatment groups in Period B and the change over time.

At the conclusion of Period A (four months), treatment with ORENCIA demonstrated significant improvements on all patient reported measures. Improvements in CHQ scores were significant in 14 out of 15 health domains measured (as measured by 95 percent confidence intervals). The greatest CHQ improvements were seen in the physical domain, which consists of physical functioning, bodily pain, role-physical and general health. With ORENCIA, pain was significantly reduced by Day 15 of Period A (-5.9 points; as measured by 95 percent confidence intervals) and was further reduced by the end of the period (-18.7 points; as measured by 95 percent confidence intervals). On the CSHQ, the sleep problem index decreased significantly by 1.86 points (p-value less than 0.05).

At the end of Period B, most ORENCIA patients maintained or continued these HRQoL improvements in 10 of the 15 CHQ health domains, while placebo patients generally experienced declining HRQoL (in 13 of 15 CHQ health domains), increased pain (+8.4 points; as measured by 95 percent confidence intervals) and sleep problems (+1.2 points; as measured by 95 percent confidence intervals).

Additional data from this study will also be presented at the ACR Annual Scientific Meeting by Tracy Li, Ph.D, director, Global Health Outcomes, Bristol-Myers Squibb, on Wednesday, October 29, at 8 a.m. (Pacific Time). Dr. Li's presentation, which will look at the real-life impact of ORENCIA® (abatacept) on JIA patients and their parents, is entitled "Reduction in Missed School Days and Improvements in Parent Activity Participation in Children with Juvenile Idiopathic Arthritis Treated with Abatacept."

About ORENCIA® (abatacept)

ORENCIA is a prescription medicine that is used to treat adults with moderate to severe RA including those who have not been helped enough by other medicines for RA. ORENCIA may prevent further damage to bones and joints, and may help the individual's ability to perform daily activities. In adults, ORENCIA may be used alone or with disease-modifying anti-rheumatic drugs (DMARDs) other than tumor necrosis factor (TNF) antagonists.

ORENCIA also reduces signs and symptoms in children and adolescents six years of age and older with moderate to severe polyarticular JIA. In children and adolescents, ORENCIA may be used alone or with MTX.

ORENCIA should not be used with TNF antagonists and is not recommended for use with other biologic RA therapy, such as anakinra.

About Juvenile Idiopathic Arthritis (JIA)

JIA - also commonly known as Juvenile Rheumatoid Arthritis (JRA) - is the most common chronic rheumatic disease in children, and it is an important cause of short-term and long-term disability.[7] It is an autoimmune disease that causes chronic pain, stiffness and swelling of the joints,[8] which may ultimately lead to joint damage and deformities.[9] The disease usually begins before the age of 16.[10] Juvenile arthritis may affect up to one in every 1,000 children in the United States.10 ORENCIA is indicated in pediatric patients ages six years and older with moderately to severely active polyarticular JIA.2 ORENCIA may be used as monotherapy or concomitantly with MTX in pediatric patients. ORENCIA should not be used with TNF antagonists, and is not recommended for use with other biologic RA therapy, such as anakinra.

Important Safety Information About ORENCIA (abatacept)

Before receiving treatment with ORENCIA, a lyophilized powder for intravenous infusion, individuals should tell their doctor about all their medical conditions, including if they have any kind of infection even if it is small (such as an open cut or sore) or an infection that is in the whole body (such as the flu) or have an infection that will not go away or a history of infections that keep coming back. People should tell their doctor if they have had tuberculosis (TB), a positive skin test for TB, or recent close contact with someone who has had TB. If symptoms of TB occur (a dry cough that doesn't go away, weight loss, fever, night sweats), they should call their doctor right away. Before starting treatment with ORENCIA, a doctor may examine the person for TB or perform a skin test.

Individuals who have or have had viral hepatitis should tell their doctor. The doctor may want to examine them for hepatitis before using ORENCIA. People should inform their doctor if they have a history of chronic obstructive pulmonary (lung) disease (COPD). In addition, individuals should let their doctor know if they are scheduled to have surgery, or recently received a vaccination or are scheduled for any vaccination.

People should also let their doctor know if they are allergic to any of the following ingredients in ORENCIA: abatacept, maltose, monobasic sodium phosphate, or sodium chloride for administration. People who have diabetes and use a blood glucose monitor to check sugar levels should tell their doctor. The infusion of ORENCIA contains maltose, a sugar that can give falsely high blood glucose readings with some monitors on the day of the infusion. The doctor may tell them to use a different way to monitor their blood sugar levels.

Women who are pregnant, planning to become pregnant, or are thinking about becoming pregnant should tell their doctor. It is not known if ORENCIA can harm your unborn baby. Women who are breast feeding should also inform their doctor. They will need to decide to either breast-feed or receive treatment with ORENCIA, but not both.

People taking ORENCIA should notify their doctor if they are taking any other kinds of medicine, including prescription and nonprescription medicines, vitamins, and herbal supplements. It is also important for individuals to tell their doctor if they are taking other biologic medicines to treat RA or JIA such as: Enbrel(etanercept), Humira (adalimumab), Remicade (infliximab), Kineret (anakinra) or Rituxan (rituximab). You may have a higher chance of getting a serious infection if you take ORENCIA® (abatacept) with other biologic medicines.

Possible Side Effects of ORENCIA(abatacept)

ORENCIA can cause serious side effects including serious infections. People receiving ORENCIA have a higher chance of getting infections including pneumonia, and other infections caused by viruses, bacteria, or fungi. Individuals should call their doctor immediately if they feel sick or get any of the following signs of infection: fever, feel very tired, cough, feel flu-like, or warm, red or painful skin.

Allergic reactions can happen on the day of treatment or the day after receiving ORENCIA. People should tell their doctor or get emergency medical help right away if they have hives, swollen face, eyelids, lips, tongue, throat, or trouble breathing.

Certain kinds of cancer (malignancies) have been reported in people receiving ORENCIA. It is not known if ORENCIA increases the chance of getting certain kinds of cancer.

Individuals should not receive ORENCIA with certain types of vaccines. ORENCIA may cause some vaccinations to be less effective.

Respiratory problems in people with COPD. Individuals may get certain respiratory problems more often if they receive ORENCIA and have COPD, including: worsened COPD, pneumonia, cough, or trouble breathing.

The more common side effects with ORENCIA in both adults and children are headache, upper respiratory tract infection, sore throat, and nausea. Other side effects in children may include diarrhea, cough, fever, and abdominal pain.

Please see accompanying Full Prescribing Information, or visit ORENCIA or bms.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to extend and enhance human life. For more information visit bms.

References

[1] Ruperto N, Lovell DJ, Quartier P, Paz E, Rubio-P?©rez N, Silva CA, Abud-Mendoza C, Burgos-Vargas R, Gerloni V, Melo-Gomes JA, Saad-Magalh??es C, Sztajnbok F, Goldenstein-Schainberg C, Scheinberg M, Penades IC, Fischbach M, Orozco J, Hashkes PJ, Hom C, Jung L, Lepore L, Oliveira S, Wallace CA, Sigal LH, Block AJ, Covucci A, Martini A, Giannini EH. Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial. The Lancet. 2008;372:383-91.

[2] ORENCIA® (abatacept) [prescribing information], Princeton, NJ: Bristol-Myers Squibb; April 2008.

[3] Selvaag AM, Flato B, Lien G, Sorskaar D, Vinje O, Oystein F. Measuring health status in early juvenile idiopathic arthritis: determinants and responsiveness of the Child Health Questionnaire. Journal of Rheumatolgy. 2003;30:1602-10.

[4] Gutierrez-Sauarez R, Pistorio A, Cruz AC, Norambuena X, Flato B, Rumba I, Harjacek M, Nielsen S, Susic G, Mihaylova D, Huemer C, Melo-Gomes J, Andersson-Gare B, Balogh Z, De Cunto C, Vesely R, Pagava K, Romicka AM, Burgos-Vargas R, Martini A, Ruperto N. Health-related quality of life of patients with juvenile idiopathic arthritis coming from 3 different geographic areas. The PRINTO multinational quality of life cohort study. Rheumatology. 2007;46:314-20.

[5] Owens JA, Spirito A, McGuinn M. The Children's Sleep Habits Questionnaire (CSHQ): psychometric properties of a survey instrument for school-aged children. Sleep. 2000;23(8):1043-51.

[6] Gould D, Kelly D, Goldstone L, Gammon J. Examining the validity of pressure ulcer risk assessment scales: developing and using illustrated patient simulations to collect the data INFORMATION POINT: Visual Analogue scale. Journal of Clinical Nursing. 2001;10:697-706.

[7] Ravelli A. Juvenile idiopathic arthritis. The Lancet. 2007:369:767-778.

[8] Medline Plus. Juvenile Rheumatoid Arthritis. US National Library of Medicine, National Institute of Health. Available at nlm.nih/medlineplus/juvenilerheumatoidarthritis.html. Accessed March 10, 2008.

[9] Zeginni E. Association of HLA-DRB1*13 with susceptibility to uveitis in juvenile idiopathic arthritis in two independent data sets. Rheumatology. 2006;45:972-974.

[10] American College of Rheumatology Web site. Arthritis in Children. Available at:
rheumatology/public/factsheets/diseases_and_conditions/juvenilearthritis.asp Accessed October 27, 2008.

Source

Phil McNamara

bms

View drug information on Humira; Kineret; Orencia.

Arthritis Sufferers Experience Reduced Pain With Tai Chi

2011-04-27T12:00:00.021-07:00

The results of a new analysis have provided good evidence to suggest that Tai Chi is beneficial for arthritis. Specifically, it was shown to decrease pain with trends towards improving overall physical health, level of tension and satisfaction with health status.

Musculoskeletal pain, such as that experienced by people with arthritis, places a severe burden on the patient and community and is recognized as an international health priority. Exercise therapy including such as strengthening, stretching and aerobic programs, have been shown to be effective for arthritic pain. Tai Chi, is a form of exercise that is regularly practiced in China to improve overall health and well-being. It is usually preformed in a group but is also practiced individually at one's leisure, which differs from traditional exercise therapy approaches used in the clinic.

Recently, a new study examined the effectiveness of Tai Chi in decreasing pain and disability and improving physical function and quality of life in people with chronic musculoskeletal pain. The study is published in the June issue of Arthritis Care & Research. Led by Amanda Hall of The George Institute in Sydney, Australia, researchers conducted a systematic review and meta-analysis. They analyzed seven eligible randomized controlled trials that used Tai Chi as the main intervention for patients with musculoskeletal pain. The results demonstrate that Tai Chi improves pain and disability in patients suffering arthritis.

The authors state, "The fact that Tai Chi is inexpensive, convenient, and enjoyable and conveys other psychological and social benefits supports the use this type of intervention for pain conditions such as arthritis."

"It is of importance to note that the results reported in this systematic review are indicative of the effect of Tai Chi versus minimal intervention (usual health care or health education) or wait list control," the authors note. Establishing the specific effects of Tai Chi would require a placebo-controlled trial, which has not yet been undertaken.

Article: "The Effectiveness of Tai Chi for Chronic Musculoskeletal Pain Conditions: A Systematic Review and Meta-Analysis," Amanda Hall, Chris Maher, Jane Latimer, Manuela Ferreira, Arthritis Care & Research, June 2009.

Source:
Sean Wagner

Wiley-Blackwell