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
воскресенье, 3 июля 2011 г.
пятница, 1 июля 2011 г.
Rheumatoid Arthritis Patients Taking Enbrel® Keep Working For Longer
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.
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.
четверг, 30 июня 2011 г.
New Biologic Drug Is Effective Against Rheumatoid Arthritis
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
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
среда, 29 июня 2011 г.
Adalimumab Proves Effective For Children With Juvenile Rheumatoid Arthritis
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
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
вторник, 28 июня 2011 г.
Celecoxib Increases Risk Of Heart Attack, New Study Finds
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.
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.
понедельник, 27 июня 2011 г.
Cartilage Repair Hope Offered By Stem Cells Tor Arthritis Sufferers
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
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
воскресенье, 26 июня 2011 г.
Activity The Key To Managing Arthritis
"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
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
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