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.
среда, 27 апреля 2011 г.
Cause Of Cartilage Degeneration In Osteoarthritis Discovered By Scripps Research Scientists
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
"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
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
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
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
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?
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
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
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
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
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.
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
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
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
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
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
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
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
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
"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
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
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
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
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
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.
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
United States
rheumatology/
View drug information on Humira.
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
United States
rheumatology/
View drug information on Humira.
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