Winter- And Spring-Onset RA Patients Have Worse 6 Month Outcomes Than Those With Summer Onset

When a patient's first symptoms of rheumatoid arthritis (RA) occur in winter, the severity of their RA (as measured by the modified Total Sharp Score, mTSS, an assessment of erosion and joint space narrowing) was rated more severe at six months, when compared to patients whose RA first became symptomatic in summer (Odds Ratio (OR) =2.82 [1.14;7], p=0.0255). Furthermore, RA patients with their first symptoms in spring showed poorer radiographic outcome compared to summer-onset patients (OR=2.83 [1.10;7.37], p=0.0322), according to the results of a new study presented today at EULAR 2009, the Annual Congress of the European League Against Rheumatism in Copenhagen, Denmark.



Similarly, patients' mTSS after six months was worse if their first symptoms had occurred in winter (OR=2.61 [1.20; 5.71], p=0.0158) or in spring (OR=2.63 [1.13; 6.14], p=0.0025) versus autumn as the reference season. This effect was not however observed at 12 month follow up, which the study authors suggest could suggest that these initial environmental factors exert less of an effect on longer term radiographic progression.



Dr Ga?«l Mouterde, Immuno-Rheumatology Department, Lapeyronie Hospital, Montpellier, France who led the research, said: "During our study of predictors of radiographic progression, we have unveiled a distinct relationship between RA progression and seasonal onset and postulate that this could be as a result of either a vitamin D deficiency or environmental factors, such as winter viruses, influencing protein citrullination. Anti-citrullinated protein antibodies (ACPAs) are often found in the immune systems of RA patients. This finding may assist towards the identification of RA patients at a higher risk of developing structural damage, in order to propose early intensive therapy and minimise disease progression."



Of the 736 patients from the multicentre French ESPOIR cohort analysed in the study (48?±12 years of age, females 77%, mean disease duration 103+/-53 days, DAS28 5.11?±1.31, HAQ score 0.97?±0.68, CRP 21.9?±32 mg/l, HLA-DRB1*01 or 04 57.5%), those found to have anti-CCP antibodies (total n=290) were also likely to have experienced increased radiographic disease progression (defined by an increase of at least 1 point of the mTSS), than those without anti-CCP antibodies, both after six months (OR=3.73 [2.04;6.82], p

U-M Study Offers New Perspective On Nitric Oxide Signaling In Rheumatoid Arthritis

Scientists at the University of Michigan Medical School have found evidence that challenges current thinking about the cause of rheumatoid arthritis (RA), a chronic inflammatory disease that damages joints, causes pain, loss of movement, and bone deformities in 2.1 million Americans.



Published in the November 2006 issue of Arthritis and Rheumatism, results from the study could help answer questions that have puzzled scientists for more than 20 years:



Why do nearly 95 percent of RA patients have a common sequence of DNA, which scientists call a shared epitope, and why do patients with this DNA sequence have more severe forms of the disease than patients without it?



Most researchers believe that RA is an autoimmune disorder, because the shared epitope is located in an area of the human genome that codes for proteins involved in the immune system's recognition of antigens.



Antigens are like little name tags on the surfaces of cells. They help the immune system recognize what belongs in our bodies and what doesn't. The immune system will attack foreign antigens. For example, without closely matched antigens, a transplant patient's immune system will reject a donated organ.



"Although the hypothesis that RA is an autoimmune disorder is widely accepted, there is no convincing evidence that it is correct," says Joseph Holoshitz, M.D., associate professor of internal medicine at U-M Medical School who directed the study. "We see this same type of association with HLA genes in other diseases, which we know are not autoimmune diseases."



Holoshitz and his colleagues discovered that the shared epitope can trigger a signaling cascade that leads to increased production of nitric oxide in other cells. A gas produced by several types of cells in the body, nitric oxide is an important signaling molecule.



"Our findings suggest this activity is unrelated to antigen presentation," says Holoshitz. "This is the first direct evidence that the shared epitope may be responsible for the overproduction of nitric oxide seen in patients with RA."



Overproduction of NO inhibits apoptosis - the natural process that leads to cell death. Resistance to apoptosis is a common trait found in cells lining the joints of RA patients, and is believed to lead to disease symptoms.



In the U-M study, cells from individuals with the shared epitope were completely resistant to cell death when compared to samples from individuals without the shared epitope.



"It was previously postulated that nitric oxide plays a role in RA, since patients have higher levels of it in their joint tissue. When we looked at the rate of NO generation in these patients, we found that it was significantly higher for people with the shared epitope," says Holoshitz.



The findings offer scientists a new way of viewing other diseases, in addition to RA. For example, narcolepsy and certain types of leukemia are strongly associated with HLA genes, yet there is no convincing evidence that they are autoimmune diseases. According to Holoshitz, further research into HLA genes and their function could offer new insights into the cause of these diseases.



Holoshitz cautions that, although the association between the shared epitope and RA is consistently found among many ethnic groups, five to 10 percent of all RA patients are shared epitope-negative. Further studies are needed to examine other possible causes of nitric oxide overproduction in RA.







The research was supported by the National Institutes of Health, the Arthritis Foundation, and the University of Michigan Biotechnology Development Fund.



Contributing authors include first author Song Ling, Ph.D., a research investigator in the departmental of internal medicine, U-M Medical School; Angela Lai, a U-M undergraduate student; and Olga Borschukova and Paul Pumpens from the Biomedical Research and Study Center, University of Latvia.



Citation: Arthritis & Rheumatism: (54) 11, pp. 3423-3432, November 2006



Written by Rossitza Iordanova



Contact: Sally Pobojewski


University of Michigan Health System

Autoantibodies Precede Disease in Lupus Patients

CONTACT:

Susan Bettendorf

301-496-8190


A new study funded largely by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) reveals that people diagnosed with systemic lupus erythematosus (lupus) - an autoimmune disease in which the body attacks its own tissues - have autoantibodies in their blood years before the symptoms of lupus appear.


The early detection of autoantibodies - proteins that attach to the body's healthy tissues by mistake - may help in recognizing those who will develop the disease and allow physicians to monitor them before they might otherwise be noticed.



Senior author John Harley, M.D., Ph.D., of the Oklahoma Medical Research Foundation and the University of Oklahoma, and his colleagues there and in other institutions, tested blood from 130 U.S. armed forces servicemen and women, without knowing their identities, who were once healthy but later developed lupus.


Using many years of previously collected samples from the Department of Defense Serum Repository, the researchers compared samples from the lupus patients to samples from those who never developed lupus.


When testing early samples from both groups, they found that those with lupus had the autoantibodies in their blood for months to years before symptoms appeared. Some of the autoantibodies, such as antinuclear antibody, had been present longer than others.

The lupus autoantibodies, say the authors, tend to accumulate in the blood in a predictable pattern up until diagnosis, when the rate of new autoantibodies slows.



'We don't know whether the virtual halt in the accumulation of new autoantibodies is a result of therapy now typically used or whether the relative stability in the autoantibodies found after diagnosis is a feature of the natural history of lupus,' said Dr. Harley. 'Certainly, this observation reminds us of how important diagnosis is for what subsequently happens in the immune system of the patient.'



NIAMS Director Stephen I. Katz, M.D., Ph.D., said 'Identifying such patterns in disease progression may lead researchers to understand what causes autoantibodies to appear when they do and how they contribute to the disease.' NIAMS researcher Gregory Dennis, M.D., a coauthor of the study, said, 'Lupus and other autoimmune diseases often go untreated for years and are diagnosed only after damage to the body tissues has occurred. Findings such as these, which will help us identify and monitor people who may develop these diseases, are extremely valuable.'



Lupus can affect many parts of the body, including the joints, skin, kidneys, heart, lungs, blood vessels and brain. People who have lupus may have many different symptoms, but some of the most common ones include extreme fatigue, painful or swollen joints (arthritis), unexplained fever, skin rashes and kidney problems. Many more women than men have lupus.

It is three times more common in African American women than in Caucasian women and is also more common in women of Hispanic, Asian and Native American descent.



Other institutions taking part in the study included NIAMS, the Department of Veterans Affairs, Walter Reed Army Medical Center and the U.S. Army Center for Health Promotion and Preventive Medicine.

Funding was also provided by the National Institute of Allergy and Infectious Diseases and the National Center for Research Resources, both part of the Department of Health and Human Services' National Institutes of Health.



To contact Dr. Harley, call Adam Cohen at the Oklahoma Medical Research Foundation at (405) 271-7159.



The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases.

For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at niams.nih.

Discovery Hints At How Autoimmune Disease May Develop Late In Life

A St. Jude Children's Research Hospital study shows that T cells, the body's master immune regulators, do not use simple on/off switches to govern the cellular machinery that regulates their development and function. Rather, they possess sophisticated molecular controls that enable them to adjust their function with exquisite precision. Such subtle adjustment enables T cells to modulate their development and function, including avoiding autoimmunity.



In autoimmune disease, rather than attacking invading microbes, the immune system attacks the body's own organs, tissues or cells. Some 80 autoimmune diseases are known, including type 1 diabetes, multiple sclerosis, rheumatoid arthritis and lupus.



"Among the many mysteries surrounding autoimmune diseases is why they can sometimes take decades to manifest themselves," said Dario Vignali, Ph.D., associate member in the St. Jude Department of Immunology. "Our findings hint that this delayed onset could be explained by subtle defects in the molecular controls on T cells." Such T cells are white blood cells whose duties include shutting down the immune system when it has done its job and suppressing T cells that can attack the body.



Vignali is the senior author of a report on this work that appears in the advance online publication of the journal Nature Immunology.



The researchers explored the function of T cell receptors, proteins that span the cell membrane of T cells. These receptors receive outside signals that instruct T cells to develop, proliferate and transmit those signals into the cell. The St. Jude investigators sought to understand why T cell receptors need many copies of switch-like components called immunoreceptor tyrosine-based activation motifs (ITAMS). ITAMs are components of the CD3 adaptor proteins that attach to the T cell receptor and help transmit the control signals from the T cell receptor into the cell.



"The ITAMs we studied are little molecular tags inside the cell by which the T cell receptor communicates to the rest of the cell," Vignali said. "The mystery we wanted to address was why the T cell receptor needs 10 ITAMs to do its job. Why not just have a simple on/off switch?"



To explore the role of multiple ITAMs, Jeff Holst, Ph.D., the paper's first author and a St. Jude postdoctoral scientist, used a technique developed in the Vignali lab to produce mice whose T cells have variations in the number and type of functional ITAMs. The technique involved using a virus as a genetic cargo-carrier to transport genes for different combinations of normal and mutant non-functional ITAMs into the mouse cells.



The researchers found that reducing the number of normal ITAMs caused the mice to develop autoimmune disease. However, the investigators also found that some mice with fewer than normal functional ITAMs did not become sick with autoimmune disease. Vignali said this finding suggests that it is not just the number of ITAMs, but also their type that may influence T cell function.
















"We theorized that there were two possibilities why the immune system needs so many ITAMs," he said. "One is that the requirement was purely quantitative, and that the ITAMs were there for signal amplification. The second possibility is that different ITAMs do slightly different things - they do have slightly different structures, so maybe they bind to some signaling molecules better than others; and their positions in the T cell receptor are different. So, while our primary observation is that quantity is more important than ITAM type, we also found that type has some influence."



The researchers' analyses of the immune systems of the altered mice indicated that reducing the number of normal ITAMs crippled a process called "negative selection." In this process, the immune system rids itself of immature T cells that might attack the body's own cells, causing autoimmune disease. Vignali said that these findings might provide insight into how autoimmune diseases start.



"One implication of our findings is that a relatively small defect in the efficiency of signal transduction through the T cell receptor could give rise to a subtle failing in negative selection, which gives rise over a long period of time to a few overly active T cells that might initiate autoimmunity," Vignali said. "Clearly from our studies there is the possibility that you don't really need a very big reduction in T cell receptor signal strength to have a defect in negative selection."



The study also showed that different T cell functions required different numbers of functional ITAMs. "We were surprised to find that many ITAMs were required to make T cells divide and expand, but only one or two was required to make T cells secrete cytokines," Vignali said. Cytokines are soluble proteins used by cells of the immune system to communicate and send messages to one another. Vignali said these basic findings represent only the beginning of more detailed studies of the role of ITAMs in T cell function.



"We believe this idea that T cell signaling acts more like a rheostat than an on/off switch offers significant new insights into how T cell development and function is controlled," Vignali said.







Other authors include Haopeng Wang, Kelly Durick Eder, Creg Workman, Kelli Boyd, Zachary Baquet, Karen Forbes and Richard Smeyne (St. Jude); Harvir Singh, Andrzej Chruscinski and Paul Utz (Stanford University School of Medicine, Stanford, Calif.); and Nicolai van Oers (The University of Texas Southwestern Medical Center, Dallas).



This work was supported by the National Institutes of Health, a Cancer Center Support CORE grant and ALSAC.



St. Jude Children's Research Hospital



St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fundraising organization. For more information, please visit stjude/.



Source: Summer Freeman


St. Jude Children's Research Hospital

Protein Involved In Causing Gum Disease, Osteoporosis, Arthritis Identified

Investigators at Hospital for Special Surgery, collaborating with researchers from other institutions, have contributed to the discovery that a gene called interferon regulator factor-8 (IRF-8) is involved in the development of diseases such as periodontitis (gum disease), rheumatoid arthritis and osteoporosis. The study, which was published online August 30, ahead of print, in the journal Nature Medicine, could lead to new treatments in the future.



"The study doesn't have immediate therapeutic applications, but it does open a new avenue of research that could help identify novel therapeutic approaches or interventions to treat diseases such as periodontitis, rheumatoid arthritis or osteoporosis," said Baohong Zhao, Ph.D., lead author of the study and a research fellow in the Arthritis and Tissue Degeneration Program at Hospital for Special Surgery located in New York City.



Dr. Zhao initiated the study while working in the laboratory led by Drs. Masamichi Takami and Ryutaro Kamijo at Showa University, Tokyo, where much of the work was performed. Dr. Zhao completed the study and extended the work to human cells during the past year at Hospital for Special Surgery working with Dr. Lionel Ivashkiv.



Specifically, the researchers discovered that downregulation of IRF-8 (meaning that the gene produces less IRF-8 protein) increases the production of cells called osteoclasts that are responsible for breaking down bone. An osteoblast is a type of cell that is responsible for forming bone and an osteoclast is a type of cell that breaks down bony tissue (bone resorption). In humans and animals, bone formation and bone resorption are closely coupled processes involved in the normal remodeling of bone. Enhanced development of osteoclasts, however, can create canals and cavities that are hallmarks of diseases such as periodontitis, osteoporosis and rheumatoid arthritis.



Previous researchers have spent time identifying genes that are upregulated during enhanced development of osteoclasts, such as NFATc1, but few studies have identified genes that are downregulated in the process. To fill this knowledge gap, scientists at Hospital for Special Surgery, collaborating with researchers at other institutions, used microarray technology to conduct a genome-wide screen to identify genes that are downregulated during the formation of osteoclasts. They found that expression of IRF-8 was reduced by 75 percent in the initial phases of osteoclast development.



The researchers then genetically engineered mice to be deficient in IRF-8 and gave the animals x-rays and CT (computed tomography) scans to analyze IRF-8's influence on bone. They found that the mice had decreased bone mass and severe osteoporosis. Experiments demonstrated that this was due not to a decreased number of osteoblasts, but because of an increased number of osteoclasts. The researchers concluded that IRF-8 suppresses the production of osteoclasts.
















Tests in human cells confirmed these findings. This included a study that showed that silencing IRF-8 messenger RNA in human osteoclast precursors with small interfering RNAs resulted in enhanced osteoclast production. In other words, decreased IRF-8 means more osteoclasts are produced.



This led the investigators to examine the effect of IRF-8 on the activity of a protein called NFATc1 that was previously reported to interact with IRF-8. They found that IRF-8 inhibited the function and expression of NFATc1. This makes sense given that upregulation of NFATc1 is involved in triggering osteoclast precursor cells to turn into osteoclasts.



"This is the first paper to identify that IRF-8 is a novel key inhibitory factor in osteoclastogenesis [production of osteoclasts]," said Dr. Zhao. "We hope that the understanding of this gene can contribute to understanding the regulatory network of osteoclastogenesis and lead to new therapeutic approaches in the future."



Other authors involved in the study are Masamichi Takami, Ph.D., Atsushi Yamada, Ph.D., Xiaogu Wang, Ph.D., and Ryutaro Kamijo, Ph.D., from Showa University in Tokyo, Japan; Takako Koga, Ph.D., and Hiroshi Takayanagi, M.D., Ph.D., from Tokyo Medical and Dental University and the International Research Center for Molecular Science in Tooth and Bone Disease, both in Japan; Xiaoyu Hu, M.D., Ph.D., and Lionel Ivashkiv, M.D., from Hospital for Special Surgery; Tomohiko Tamura, M.D., Ph.D., and Keiko Ozato, Ph.D., from the National Institutes of Health; and Yongwon Choi, Ph.D., from the University of Pennsylvania School of Medicine.



The work was supported by in part by the High-Tech Research Center Project for Private Universities from the Ministry of Education, Culture, Sports, Science and Technology in Japan; by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science; and by grants from the U.S. National Institutes of Health.



Source:
Phyllis Fisher


Hospital for Special Surgery

Association Between Rheumatoid Arthritis And Poor Sleep In Women

According to a research abstract that will be presented on Wednesday, June 10, at SLEEP 2009, the 23rd Annual Meeting of the Associated Professional Sleep Societies, symptoms of Rheumatoid Arthritis (RA) negatively affect women's sleep. Sleep is further impaired by pain, depression and poor adherence to RA medications.



Results indicate that length of time since RA diagnosis, RA disease activity, level of pain, depression symptoms and adherence to medications for RA may cause women suffering from the disease to have poor sleep quality.



According to lead author Faith Luyster, PhD, of the University of Pittsburgh, Pa., findings emphasize the need for further research concerning poor RA medication adherence and sleep quality.



"Treating depression in women with RA may not only improve sleep but may also improve pain and adherence to medications," said Luyster.



The study involved 133 women with RA; their average age was 56 years, and they were primarily Caucasian, married, had at least a high school education, were not depressed and had RA for 14.76 years. A majority of participants (71 percent) reported poor sleep quality. Pain and depression were measured through subjective reports, and medication adherence was measured objectively with an electronic medication monitor on medication bottle caps.



Sleep disturbances and depression are more prevalent in women in the general population. According to the American Academy of Sleep Medicine (AASM), women face many challenges that interfere with their sleep quality and duration.



More information about how sleep affects women can be found at sleepeducation/Topic.aspx?id=67



Abstract Title: Sleep Quality in Women with Rheumatoid Arthritis

Presentation Date: Wednesday, June 10

Category: Sleep in Medical Disorders

Abstract ID: 1007



Source:
Kelly Wagner


American Academy of Sleep Medicine

News From The Annals Of Internal Medicine, 18 August 2009

1. Chinese Herbal Remedy Shows Promise for Treating Rheumatoid Arthritis



Rheumatoid arthritis is an autoimmune disease that causes painful and debilitating swelling of the joints. Physicians often prescribe anti-inflammatory drugs such as sulfasalazine for the initial treatment of rheumatoid arthritis. Despite the clinical efficacy of these types of drugs, many patients discontinue treatment due to lack of improvement or adverse events. The Chinese herbal remedy Tripterygium wilfordii Hook F (TwHF) (also known as "lei gong teng" or "thunder god vine") has shown promise in treating autoimmune and inflammatory conditions. Researchers randomly assigned 121 patients to take either TwHF root extract 60mg three times per day or sulfasalazine 1g two times per day for 24 weeks. The researchers used a standard measure of joint involvement to determine treatment outcomes. Many patients in both groups discontinued treatment. However, among those who continued treatment for 24 weeks, improvement was greater with TwHF (67%) than with sulfasalazine (36%) and adverse event rates were similar. The resulst were similar in analyses that adjusted for patient drop-out. Researchers conclude that the rapid improvement in joint symptoms may make TwHF extract an attractive and affordable alternative to anti-inflammatory drugs.



2. Elective Induction of Labor May Reduce Cesareans, Improve Fetal Outcomes



Elective induction of labor, or labor that is induced without medical necessity, is rapidly increasing in the United States. Pregnant women who are at term and their physicians may consider labor induction for several reasons including physical discomfort, scheduling issues, or concerns about maternal or fetal complications. However, many experts discourage the practice because of the widely held belief that it increases the risk for cesarean delivery and other complications. Researchers conducted a systematic review of 11 randomized trials and 25 observational studies to compare the benefits and harms of elective induction of labor and expectant management of pregnancy. The researchers found that elective induction of labor at 41 weeks of gestation and beyond was associated with an approximately 20 percent reduction in the rate of cesarean delivery and a 50 percent reduction in the presence of meconium in the amniotic fluid. These results suggest that outcomes may be better with elective induction of labor. More research should be conducted before elective induction of labor is routinely adopted.



3. China's National Free Antiretroviral Program Has Limited Success, Shows Need for Improvement



In 2002, China began the National Free Antiretroviral Program to provide highly active antiretroviral therapy (HAART) to eligible patients with HIV. To determine the long-term outcomes of the program, researchers collected information on patient deaths and CD4 cell counts for the 48,785 program participants over five years. They found that mortality was highest within the first three months after HAART initiation. After about six months of treatment, death rates decreased to levels similar to those seen in HIV-infected patients who receive HAART in other developing countries. The lower death rates remained stable through year five. However, about half of the patients in the program had CD4 cell counts that suggested treatment failure after five years. The researchers believe that treatment failure may be due to the limited number of drug choices available to these patients. Once resistance developed, patients had few options for other drugs they could take.



Source:
Angela Collom


American College of Physicians

New Way Of Classifying Rheumatoid Arthritis Aimed At Identifying The Disease Earlier

The American College of Rheumatology today announced the release of revised classification criteria (created in collaboration with the European League Against Rheumatism) for rheumatoid arthritis, which will allow the study of treatments for RA at much earlier stages of the disease - before joint damage occurs - ultimately leading to better patient outcomes.



Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in the organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.



Classification criteria are the standard and accepted means by which researchers define a disease. They allow researchers to define individuals as having or not having a given disease, helping to standardize recruitment into clinical trials and other research studies. Although not intended as criteria for diagnosis in clinical practice, with some additional research, classification criteria may be modified and adopted for such use.



Classification criteria are typically updated as knowledge changes, which is the case with the new RA criteria - published in the College's journal, Arthritis & Rheumatism. The previous criteria were created in 1987. Since that time, new therapies have emerged that can prevent joint damage in people with RA. With these modern therapies, the goal of treatment is to prevent people from reaching the point where their RA is causing chronic damage to their joints.



"The 1987 criteria actually posed a major barrier to the study of treatments designed to prevent joint damage in RA," explains Gillian Hawker, MD; senior author of the new criteria. "Many patients did not fulfill the previous RA classification criteria until their disease was well-advanced, and - in many cases - joint damage had already occurred. This truly limited RA researchers from studying the disease at its earlier phases, which is critical to the development of new treatments to prevent damage."


In 2008, the ACR began a collaborative project with the EULAR to create the first new set of RA classification criteria in over 20 years. To establish the new criteria, researchers completed three phases of work. The first phase (led by EULAR) involved reviewing existing data collected from patients with early arthritis to determine which factors best identified patients who were, according to Daniel Aletaha, MD, MS; lead author of this phase of research, "at a high risk of developing the more persistent and erosive arthritis that we currently consider to be RA." Dr. Aletaha also explains that this phase of research is an important component to the overall project as "all classification criteria need to be built on scientific evidence, either from the literature or - as with these criteria - from extensive analysis of real patient data."
















The second phase of work (led by the ACR) was aimed at reaching consensus among practicing rheumatologists on which factors were most important in determining a person's likelihood of developing the chronic joint damage that has been known for many years as the hallmark of RA. "Both scientific evidence and the experience of RA experts needed to be considered in the development of the new criteria to ensure all important factors were identified," explains criteria author Tuhina Neogi, MD, PhD. "Additionally, ensuring the new criteria reflects the opinions of front-line rheumatologists diagnosing and treating patients in clinical practice is key to their ultimate acceptance."



In phase three, researchers integrated the findings from the first two phases of work, refined a scoring system, and determined the optimal cut off point to define the disease. Patients to whom these criteria should be applied must have confirmed presence of joint swelling, indicating synovitis - the inflammation of the synovial membrane, which lines a joint - in at least one joint, and no other possible diagnosis that might better explain the symptoms (such as lupus or gout).



"To be classified as having 'definite RA,' patients must receive a score of six or greater (out of a possible 10)," explains Alan Silman, MD who initiated the project. "The scoring system takes into consideration the number and site/size of involved joints, laboratory tests of inflammation and auto-immunity, and symptom duration."



Researchers continue to make great strides in RA research. The creation of this new set of classification criteria is expected to further accelerate the research being done in this field. The next logical step, according to Dr. Hawker, is to use these classification criteria as the basis for the development of diagnostic criteria for RA, for use by practicing rheumatologists.



"Under the correct circumstances, new knowledge resulting from rheumatology research can quickly move into applicable treatments for patients," explains ACR President Stanley B. Cohen, MD. "We believe these new classification criteria will open the door to more meaningful studies of RA and will eventually lead to changes in the diagnosis and treatment of the disease. This is an important step for RA researchers, practicing rheumatologists and patients."


"2010 Rheumatoid Arthritis Classification Criteria: An American College of Rheumatology/European League Against Rheumatism Collaborative initiative."
Daniel Aletaha, Tuhina Neogi, Alan J. Silman, Julia Funovits, David T. Felson, Clifton O. Bingham, III, Neal S. Birnbaum, Gerd R. Burmester, Vivian P. Bykerk, Marc D. Cohen, Bernard Combe, Karen H. Costenbader, Maxime Dougados, Paul Emery, Gianfranco Ferraccioli, Johanna M. W. Hazes, Kathryn Hobbs, Tom W. J. Huizinga, Arthur Kavanaugh, Jonathan Kay, Tore K. Kvien, Timothy Laing, Philip Mease, Henri A. M?©nard, Larry W. Moreland, Raymond L. Naden, Theodore Pincus, Josef S. Smolen, Ewa Stanislawska-Biernat, Deborah Symmons, Paul P. Tak, Katherine S. Upchurch, Jir?‡?­ Vencovsky??, Frederick Wolfe, and Gillian Hawker.

Arthritis & Rheumatism; Published Online: August 9, 2010 (DOI: 10.1002/art.27584); Print Issue Date: September 2010.

Knee Arthritis Adversely Affected By Obesity

New studies will help patients better understand the role that obesity plays in knee arthritis and recovery from knee surgery



More than 14 million visits were made to physicians' offices in 2008 by patients with knee problems. Five new studies presented at the 2011 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS) look at the effect that obesity has on knee arthritis and a patient's ability to recover from knee surgery.



Does Obesity Cause Irreparable Damage To Knees Despite Weight Loss?



One new study found that while weight loss via bariatric surgery may improve knee pain in obese patients with knee osteoarthritis, there may be permanent damage to the knee from being morbidly obese.



The investigation included 10 morbidly obese patients with knee osteoarthritis who were evaluated before and after bariatric surgery. Patients lost an average of 51 pounds in one year. One year after surgery, knee pain and function improved significantly.



"For a long time people felt there was nothing they could do to mitigate the debilitating effects of knee arthritis, but now we know that surgically-assisted weight loss is a way that folks can help themselves," says Michael S. Sridhar, MD, co-investigator and resident at Emory University. "However, there is probably some element of irreparable damage from being morbidly obese that may constrain the improvement in knee pain despite significant weight loss. Looking at the actual joint surfaces with advanced imaging to assess damage is the exciting next step in studying the evolution of knee arthritis in the obese population."



Are 'Super-Obese' Patients At Greater Risk For Post-Surgery Complications?



Also, two new studies just released examine whether obesity contributes to greater complications after hip and knee replacement surgery. The first study considers patients in the "super obese" category who have a body mass index (BMI) greater than 45. Few studies have examined whether complication rates for total joint replacement (TJR) patients may increase for "super-obese" patients.



This study compared the outcomes after TJR in 137 "super-obese" patients versus 63 non-obese patients.



Ran Schwarzkopf, MD, co-investigator and chief resident, New York University Hospital for Joint Diseases, and his research team found that the number of overall complications were significantly higher for the "super-obese" compared to non-obese. Among "super-obese" patients, each 5-unit increase in BMI over 45 was associated with a statistically significant increased risk of having in-hospital and post-operative outpatient complications or readmission. Also, days to discharge were found to increase by almost 14 percent for each 5-unit increase in BMI over 45.



The second study analyzed complication rates for morbidly obese patients (BMI greater than 40) after TJR. The study reviewed data from 12,355 patients and compared complication rates in morbidly-obese patients versus normal-weight patients.
















Led by Richard J. Friedman, MD, FRCSC, co-investigator and Chairman, Department of Orthopaedic Surgery, Roper Hospital, Charleston, SC, the study found that morbid obesity contributed to a significantly higher incidence of complications such as redness around the surgical wound, swelling of the legs, bacterial infections, respiratory disorders, neurologic and gastrointestinal complications and cardiac arrhythmias following total hip and knee replacements.



Will Isolated Weight Loss Improve Knee Pain and Movement?



Another new study just released analyzed the effects of isolated weight loss via bariatric surgery on knee osteoarthritis. The study involved 24 obese patients with knee osteoarthritis who were scheduled to undergo bariatric surgery. Patient weights and knee symptoms were recorded before the surgery and 6 and 12 months after surgery. Patients were not prescribed exercise or physical therapy, anti-inflammatory medications or knee injections post-operatively.



The study found that isolated weight loss following bariatric surgery resulted in significant improvements in knee pain, stiffness and function.



"Other studies have looked at the effect that a combination of weight loss, diet and exercise had on knee arthritis, but it was difficult to say which of these factors contributed the most to reducing knee pain," says Christopher Edwards, co-investigator and a fourth year medical student at the Penn State College of Medicine. "Our study should send a message to patients, health care providers, and payers that weight loss is an important consideration in the treatment of knee arthritis."



Can We Explain the Dramatic Rise in TKR Rates in the US by Population Size and the Obesity Epidemic?



Elena Losina, PhD, co-director, Orthopedics and Arthritis Center for Outcomes Research at Brigham and women's Hospital Associate and Professor of Orthopedic Surgery, Harvard Medical School , led a research team to examine trends in total knee replacement (TKR) utilization and found that it doubled during the decade from 1997-2007. The proportion performed in younger groups tripled. The proportion of obese persons increased by about 15 percent between 1997 and 2007. Such an increase in the obesity epidemic could explain about 20 percent of the increased utilization of TKR. Data suggests that expanding the indications for TKR in younger ages (due to sport-related injuries, obesity and as a consequence, early onset of osteoarthritis) is the likely explanation for the dramatic increase in TKR rates in the US.



Disclosures: The authors for these five studies do not have anything related to disclose.



Source:
American Academy of Orthopaedic Surgeons

FDA Announces Dates for Public Meeting on Non-Steroidal Anti-Inflammatory Drugs

The Food and Drug Administration (FDA) has announced a joint public meeting of the agency's Arthritis Advisory Committee
and the Drug Safety and Risk Management Advisory Committee to be held February 16, 17 and 18, 2005.


The committees will discuss the overall benefit-to-risk considerations (including cardiovascular and gastrointestinal
concerns) for COX-2 selective non-steroidal anti-inflammatory drugs (NSAIDs) and related medicines.


Members of the public are encouraged to participate in this meeting. Interested persons may present data, information or
views, orally or in writing, on issues pending before the committees. Oral presentations from the public will be scheduled
between 1:00 p.m. and 3:00 p.m. on February 17. Time allotted for each presentation may be limited. Those desiring to make
formal oral presentations should register to speak at the meeting before February 4, 2005. No registration is required for
those only planning on attending the meeting.


The three-day meeting will be held at the Hilton Washington DC North, 620 Perry Parkway, Gaithersburg, Md. The proceedings
will start at 8:00 a.m. each day. Agendas and other background materials will be posted online no later than one business day
before the meeting.


For more information regarding this meeting, including contact information for members of the public interested in making
presentations or submitting written comments please CLICK HERE.


Media Inquiries: 301-827-6242

Consumer Inquiries: 888-INFO-FDA

This is an FDA Press Release

PsoriasisDX Genetic Test For Psoriatic Arthritis Now Available In Europe As A CE Marked In Vitro Diagnostic Medical Device

Molecular dermatology research and development innovator DermaGenoma, Inc. today announced that the PsoriasisDX Genetic Test for Psoriatic Arthritis (PsA) is now available as a CE Marked product under the European In Vitro Diagnostic Directive.


CE Marking is required for certain product groups to indicate conformity with the essential requirements set out in European Directives. The PsoriasisDX Genetic Test for Psoriatic Arthritis complies with the essential requirements of the European IVD Directive.


The PsoriasisDX Genetic Test helps identify those at high risk for developing Psoriatic Arthritis before they experience arthritic symptoms, providing the opportunity to lessen joint damage through early medical intervention.


"We are excited to extend this revolutionary genetics testing breakthrough to dermatologists in Europe," says Andy Goren, CEO of DermaGenoma, Inc. "It helps doctors determine the proper treatments for patients."


Source:

DermaGenoma, Inc.

Blood Clotting Protein Linked To Rheumatoid Arthritis

Researchers at Cincinnati Children's have issued the first study showing that a protein normally involved in blood clotting (fibrin), also plays an important role in the inflammatory response and development of rheumatoid arthritis. Inflammatory joint disease appears to be driven by the engagement of inflammatory cells with fibrin matrices through a specific integrin receptor, aMB2. Writing in the November issue of The Journal of Clinical Investigation, researchers suggest that therapies designed to interrupt the localized interaction of inflammatory cells and fibrin may help arthritis patients.


"Our study establishes that fibrin is a powerful, although context dependent, determinant of inflammatory joint disease," said Jay Degen, Ph.D., a researcher in Developmental Biology at Cincinnati Children's and the study's lead author. "These findings also suggest that pharmacologically interrupting the interaction of fibrin and aMB2 might be efficacious in the treatment of arthritic disease as well as many other inflammatory diseases, such as multiple sclerosis."


Affecting 2.1 million people in the United States, rheumatoid arthritis is a painful and debilitating disease involving chronic inflammation, tissue degeneration, loss of cartilage and bone and ultimately loss of joint mobility and function, according to the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Although the disease's precise cause is not fully known, activation of specific components in the body's immune system seem to play a major role in its onset and early progression, according to researchers. Fibrin deposits are a prominent feature of arthritic joints and the protein appears to be a link between systems that control inflammation and bleeding within joints. Dr. Degen and his colleagues explained that in arthritic joints, the mesh-like matrices formed by fibrin to create blood clots may control local activity of inflammatory cells as well as support inappropriate tissue reorganization.


The study was conducted by a team that includes researchers from Cincinnati Children's and the University of Cincinnati's College of Medicine using genetically engineered mice with collagen-induced arthritis of the knee and paw. The mice were designed to have selective alterations in the production of fibrinogen, a precursor to fibrin, to allow researchers to evaluate the inflammatory impact of fibrin, especially as it interacts with aMB2.


The study was supported by a grant from the National Institutes of Health and the Arthritis Foundation. Dr. Degen and the research team are continuing their research to determine more definitively how the interruption of fibrin and aMB2 might translate into potential therapeutic treatment for patients.


Cincinnati Children's, one of the top five children's hospitals in the nation according to Child magazine, is a 475 bed institution devoted to bringing the world the joy of healthier kids. Cincinnati Children's is dedicated to providing care that is timely, efficient, effective, family-centered, equitable and safe. For its efforts to transform the way health care is provided, Cincinnati Children's received the 2006 American Hospital Association McKesson Quest for Quality Prize®. Cincinnati Children's ranks second nationally among all pediatric centers in research grants from the National Institutes of Health and is a teaching affiliate of the University of Cincinnati College of Medicine. The Cincinnati Children's vision is to be the leader in improving child health.


Cincinnati Children's Hospital Medical Center

3333 Burnet Ave.

Cincinnati, OH 45229-3039

United States

cincinnatichildrens

A Bit Of Reassurance On Lyme Disease

Tick bites generate fears of Lyme disease in every parent, but this study of
99 children finds that one of Lyme's complications -- arthritis -- has a
good prognosis. Researchers led by Robert Sundel, MD, a rheumatologist at
Children's, found that 77 percent of children were cured with less than 3
months of antibiotic treatment. The remainder were also ultimately relieved
of their arthritis, though additional treatment (usually one month of
intravenous antibiotics) was required. As long as children were treated
until joint inflammation was fully controlled, there were no long-term
problems.


Children's Hospital Boston is home to the world's largest research
enterprise based at a pediatric medical center, where its discoveries have
benefited both children and adults since 1869. More than 500 scientists,
including eight members of the National Academy of Sciences, 11 members of
the Institute of Medicine and 12 members of the Howard Hughes Medical
Institute comprise Children's research community. Founded as a 20-bed
hospital for children, Children's Hospital Boston today is a 397-bed
comprehensive center for pediatric and adolescent health care grounded in
the values of excellence in patient care and sensitivity to the complex
needs and diversity of children and families. Children's also is the primary
pediatric teaching affiliate of Harvard Medical School. For more information
about the hospital and its research visit:
childrenshospital/newsroom.

Children's Hospital Boston

Geisinger Researchers Awarded Funds For Personalized Healthcare Project

Researchers at Geisinger Medical Center recently received funding totaling more than $44,000 from a Geisinger Health System (GHS) - NYU Langone Medical Center (NYULMC) collaborative project focusing on personalized healthcare.


The grant, titled "Expanding Comparative Effectiveness Research in Orthopedics by Capturing Uniform Measures of Patient-Reported Functional Outcomes at Two Institutions", will permit Geisinger to administer electronic questionnaires to patients with osteoarthritis (OA) via new, touch-screen monitors in its orthopaedic clinics. Results from these questionnaires will allow physicians to track patient-reported outcomes, which are critical in developing evidence-based protocols in OA management.


"There is an urgent need to create evidence-based guidelines to assist health care providers in managing osteoarthritis. By integrating an electronic questionnaire into patient visits, we can collect valuable data regarding the effectiveness of our treatments and use that feedback to determine what's working well and what we can improve," said Wade Smith, Chairman, Orthopaedics, Geisinger Health System.


By partnering with NYULMC, data will be collected from two very divergent populations, allowing for interinstitutional research and collaboration. Both institutions will integrate the data into electronic health record systems.


"Our ultimate goal is to include patient-centered outcome data as an automatic part of the medical record here at Geisinger," Dr. Smith said. "This grant is the first step toward realizing that goal, which would be a transformative change in our ability to continually improve how we care for osteoarthritis patients."


Source

Geisinger Health System

Funding For Building Better Bones And Tissue In The Lab

Tissue engineering holds great promise for the treatment of conditions such as arthritis, osteoporosis, fibrosis, periodontal disease and traumatic injuries. However, bone and cartilage currently produced in the laboratory don't have sufficient strength to function in the body so they're not clinically viable. Dr. Douglas Hamilton, a dental researcher with the Schulich School of Medicine & Dentistry at The University of Western Ontario has received funding from the Canada Foundation for Innovation (CFI) to try to find solutions to that problem.



Hamilton and the Centre for the Study of Biomaterials and Tissue Regeneration has received nearly $163,000 from CFI to purchase specialized equipment to assess cell responses to a variety of mechanical forces and biomaterial types using state-of-the-art molecular biology and imaging techniques.



"In many instances our ability to help tissues such as bone to repair, is limited as we don't fully understand how human tissues respond to the presence of artificial materials. This becomes even more problematic in tissues that are loaded due to normal human activity," says Hamilton. "With the funding from the CFI, we are establishing an innovative laboratory that will allows us to study how cells respond to both mechanical stimulation and biomaterials such as titanium at the same time. We anticipate learning much about how cells sense their environment and subsequently regenerate tissues, which will be important in orthopaedics, dentistry, and cardiovascular medicine."



CFI just announced $45.5 million in new funds to support 251 projects across the country. Western received a total of $1.3 million to fund five research projects. The four other recipients are:
Dr. Timothy Regnault, Obstetrics and Gynaecology, Schulich School of Medicine & Dentistry, $288,000, A Laboratory for Investigating the Role of Fetal Programming in Metabolic Syndrome. Regnault is also a scientist with the Lawson Health Research Institute.


Dr. Joan Knoll, Department of Pathology, Schulich Medicine & Dentistry, $212,039, Translational Cytogenomic Infrastructure for Detection and Characterization of Chromosomal Abnormalities. Knoll is also an associate scientist at Lawson.


Dr. Samuel Siu, Department of Medicine, Schulich Medicine & Dentistry, $359,419, Translational Imaging Centre for Cardiovascular Outcomes Research (TRICORE). Siu is the Chair and Chief of Cardiology.


Desmond Moser, PhD, Earth Sciences, Faculty of Science and Geography, Faculty of Social Sciences, $310,051, Nanobeam Materials Analyzer for Probing Planetary Evolution and Resources (NanoMAPPER); an Innovation in Planetary Materials Science





The CFI is an independent corporation created by the Government of Canada to fund research infrastructure. A complete list of funded projects can be found at innovation.ca.



Source: Kathy Wallis


University of Western Ontario

Long-Term Follow-Up Data Confirm Cox-2 Inhibitor Rofecoxib Substantially Increases Risk Of Stroke, Heart Attack, And Death

Long term follow-up data from the APPROVe trial confirms that use of the Cox-2 inhibitor rofecoxib* substantially increases the risk of stroke, heart attack and death compared with placebo. These are the conclusions of an Article published early Online and in an upcoming edition of The Lancet. The paper was written by Professor John A Baron, Dartmouth Medical School, Lebanon, New Hampshire, USA, Dr Robert Bresalier, MD Anderson Cancer Center, University of Texas, USA, and Professor Dion Morton, University of Birmingham, UK and colleagues.


The APPROVe study was a randomised, placebo-controlled trial, which aimed to assess the effects of 3-year treatment with rofecoxib on recurrence of cancerous polyps in the bowel. The study looked at 2587 patients from 108 centres worldwide during 2000 and 2001, and patients were initially monitored for adverse events only while on treatment and for 14 days afterwards. In this paper, the researchers attempted to follow-up for one year all patients that had had to stop treatment because of cardiovascular toxicity. The end-point studied was the combined incidence of non-fatal heart attack, non-fatal stroke, and death from cardiovascular, haemorrhagic, or unknown causes (the Antiplatelet Trialists' Collaboration [APTC] combined endpoint).


Follow-up data were obtained for 84% of participants, and the researchers found that the relative risk of reaching APTC was increased by 79% in the rofecoxib group compared with placebo. This was consistent with earlier findings of increased risk while on treatment or 14 days afterwards, in which the relative risk of reaching APTC was more than doubled (a 112% increased risk). In terms of the individual outcomes after one-year follow up, the risk of heart attack or stroke was roughly doubled for rofecoxib patients compared with placebo, while the relative risk of death increased by 31%. There was no substantial change in the increased relative risk of cardiovascular events over time.


The authors conclude: "Our data are compatible with an early increase in risk that seems to persist for about 1 year after 3 years of treatment. The cardiovascular toxicity seems to be a class effect; indeed, studies of other selective COX-2 inhibitors have reported similar findings. Conventional non-aspirin NSAIDs??  may share the same toxicity to the extent that they are COX-2 selective. All these drugs are effective analgesic and anti-inflammatory agents, and seem to reduce risks of colorectal neoplasia. However, these benefits will have to be weighed against their proven or possible cardiovascular risks in assessing their suitability in various clinical settings."


In an accompanying Comment, Dr Colin Baigent, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, UK, and Dr Carlo Patrono, Catholic University of Rome, Italy, say: "The results of randomised trials are consistent with all coxibs having some vascular risk, but also with some traditional NSAIDs carrying similar risks. Switching from a coxib to a traditional NSAID will not necessarily avoid these vascular hazards, but will result in a two-to-three-fold increase in the risk of a serious upper gastrointestinal complication - ie, perforation, obstruction, or bleed. A physician choosing between alternative anti-inflammatory regimens for a patient needs to be able to weigh each regimen's hazards, especially cardiovascular and gastrointestinal risks." They add that further research is needed to create a validated method for estimating the risk of a serious gastrointestinal complication.















*In 2004, Merck voluntarily withdrew rofecoxib (Vioxx) from the market because of concerns about increased risk of heart attack and stroke associated with long-term, high-dosage use.

?? NSAID=Non-steroidal anti-inflammatory drug.


Article

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

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

The Lancet - October 14, 2008DOI:10.1016/S0140-6736(08)61490-7

Click here to view Summary online (no login required)


Comment

"Selective COX-2 inhibitors: where do we go from here?"

Colin Baigent, Carlo Patrono

The Lancet -10.1016/S0140-6736(08)61491-9

Click here to see Full Comment (login required)


View drug information on Vioxx.

Success in Treatment of Children with Juvenile Arthritis

In the May 2, 2005, issue of The Journal of Experimental Medicine, Virginia Pascual, MD, and Jacques Banchereau, Ph D,
from the Baylor Institute for Immunology Research in Dallas (BIIR), report on the successful treatment of children with
systemic onset juvenile idiopathic arthritis (SoJIA). The findings are highly significant for SoJIA patients for whom
previous therapies have failed.


Approximately 250,000 children in the U.S. suffer from juvenile arthritis. SoJIA accounts for about 10 percent of all
juvenile arthritis cases with unknown causes. Early symptoms, which often go undiagnosed, may include fever and a rash. As
the disease progresses, anemia and other blood-related issues develop, as do inflammation and joint pain. Depending on the
duration and severity of the disease long-term disabilities may develop.


"Most of the children in our study have suffered from persistent fever and arthritis for years. Additionally, they have
suffered from side effects resulting from conventional medications. Through this research, we found that we could not only
control the disease, but also allow these children to grow and carry out normal lives," said Dr. Pascual.


In collaboration with researchers from Texas Scottish Rite Hospital for Children in Dallas, the BIIR team identified children
with this form of juvenile arthritis who had not responded to other treatment regimens. They discovered that white blood
cells from these SoJIA patients expressed higher levels of certain immune system genes than white blood cells from healthy
individuals. They also found that blood serum from the SoJIA patients caused healthy white blood cells to start
overexpressing these genes and to secrete higher levels of interleukin-1b. Interleukins are proteins made by white blood
cells that help regulate the immune system. The researchers observed that higher IL-1b secretion also occurred in SoJIA
patients.


"We felt that oversecretion of IL-1b might play a significant role in SoJIA and that inhibiting IL-1b activity could be
beneficial," said Dr. Banchereau, director, BIIR.


To test this hypothesis, nine SoJIA patients received a drug, called Anakinra, which inactivated IL-1. Anakinra, marketed by
Amgen, is a genetically engineered version of the IL-1 receptor that has been used to treat rheumatoid arthritis. All nine
patients responded to the therapy. Seven patients had systemic symptoms, such as fever. A week after the first treatment the
fever was gone from all seven and did not return for the length of the one-year follow up. Eight of the nine had active
arthritis. In these patients, the researchers observed decreases in the arthritic symptoms in the joints as well as
improvement of hemoglobin levels, white blood cell count and a number of other indicators of arthritis. They found that the
therapy completely restored the function of six of the eight patients and lessened the symptoms of the remaining two.



The findings were also presented by Dr. Pascual at the recent Federation of Clinical Immunology Societies Meeting held in
Boston.


Dallas-based Baylor Institute for Immunology Research is the immunology research component of Baylor Research Institute, an
affiliate of Baylor Health Care System. Opened in 1996, Baylor Institute for Immunology Research brings laboratory scientists
and clinicians together in an effort to increase understanding of how the immune system works. The institute is devoted to
translating basic laboratory discoveries made about the immune system into effective treatments for humans. This
interdisciplinary program focuses on developing new therapies, such as dendritic cell therapy, which involves the use of
dendritic cells to modulate the immune response in beneficial ways to treat cancer, infectious diseases, autoimmune diseases,
and transplant rejection.


For more information about Baylor Institute for Immunology Research, visit baylorhealth.

Orencia(R) (Abatacept) Demonstrates Consistent Safety And Effectiveness Over 7 Years

Bristol-Myers Squibb Company (NYSE: BMY) announced results of two ORENCIA® (abatacept) studies at the 2009 Annual European Congress of Rheumatology (EULAR) currently being held in Copenhagen, Denmark.



I. Phase IIb 100 trial (7 years)[1]


The first, a long-term extension (LTE) study, analysed ORENCIA's safety and efficacy profile over 7 years of treatment in rheumatoid arthritis (RA) patients who have had an inadequate response to methotrexate (MTX).



Study design


During the 1 year randomised, double-blind (DB) placebo controlled period of this Phase IIb study, 339 patients with active RA and an inadequate response to MTX were randomised to receive either ORENCIA plus MTX or placebo plus MTX. On completion of the DB period, 219 patients entered the open-label LTE, receiving a fixed dose of ORENCIA 10 mg/kg (according to weight range) plus MTX every 4 weeks. During the LTE, safety assessments were performed once a month, and efficacy assessments quarterly.



Outcomes


During the LTE, treatment with ORENCIA and MTX in combination was generally well tolerated, with no increase in the frequency of safety events over time. The cumulative incidence of adverse events (AEs) was 366.1 per 100 patient years, serious AEs was 17.4 per 100 patient years and serious infections was 3.18 per 100 patient years. These data are consistent with previous data on ORENCIA in combination with MTX.



After 7 years, over half (52.1%) of ORENCIA patients (n=85) entering the LTE period remained on treatment. Over this 7 year period, discontinuations due to lack of efficacy and AEs were 11.0% and 19.2%, respectively.



While the LTE was principally designed to examine the long-term safety of ORENCIA, efficacy data were also collected (as observed) in those patients who remained in the LTE. At 7 years, of those patients still on ORENCIA (n=85):


- 69.7% achieved a low disease activity score (LDAS)

- 51.5% achieved remission (DAS28-CRP defined)

- 51.4% achieved an ACR 70 score



"The relevance of these long-term data should not be underestimated for a chronic and progressive disease such as rheumatoid arthritis," commented Professor Ren?© Westhovens, University Hospital Leuven, Belgium. "These patients have to live with the disease, and in many cases, undergo treatment, for the rest of their lives. For both patients and clinicians therefore, it is important that a treatment has a proven long-term safety and efficacy profile.



As part of a comprehensive clinical trial programme, ORENCIA's safety profile has already been studied through more than 10,000 patient years of exposure. These new data further reinforce ORENCIA, in combination with MTX, as a proven treatment option for moderate to severe active RA in adult patients who have had an insufficient response or intolerance to other disease-modifying anti-rheumatic drugs, including at least one tumour necrosis factor (TNF) inhibitor.[2]
















II. AIM trial (5 years)[3]


The second study, also presented in Copenhagen this week is the AIM (Abatacept in Inadequate responders to Methotrexate) study LTE, which reinforces the long-term safety and efficacy profile of ORENCIA.



Study design


Of the 433 ORENCIA and 219 placebo treated patients who completed the 1 year, randomised DB, placebo controlled AIM trial, 378 ORENCIA and 161 placebo treated patients entered the open-label LTE period, receiving ORENCIA [~10 mg/kg] plus MTX.



Outcomes: efficacy & safety


ORENCIA patient retention rates remained high in the AIM LTE, with 70.4% of patients (n=266/378) remaining on treatment with ORENCIA plus MTX at year 5. Of these, 33.7% achieved clinical remission (DAS28 defined), and ACR 20, 50 and 70 response rates were 83.6%, 61.1% and 39.6%, respectively, at 5 years.



The types and incidence of AEs and serious AEs were similar between the DB and cumulative (combined DB + LTE) phases. During the DB phase, incidence rates of AEs were 303.4 per 100 patient years and serious AEs, 17.7 per 100 patient years. During the cumulative phase, incidence rates of AEs were 242.3 per 100 patient years and serious AEs, 13.9 per 100 patient years. Incidence rates of serious infections were 4.2 per 100 patient years in the DB period and 2.8 per 100 patient years in the cumulative phase.



Outcomes: inhibition of structural damage progression[4]


X-ray data from the AIM LTE, also presented at EULAR this week, demonstrated that over 5 years, ORENCIA inhibited structural damage progression in the majority of patients on treatment. 45.1% of patients (n=120) assessed at year 5 continued to show no progression in structural damage. 98% of patients who were non-progressors during years 1-4 remained non-progressors at year 5.





About ORENCIA



ORENCIA is a selective co-stimulation modulator of T-cell activation. ORENCIA is designed to prevent full T-cell activation and inhibit the release of chemicals leading to joint inflammation and destruction as observed in RA.[5]



ORENCIA is the first biologic discovered and developed in Bristol-Myers Squibb research centres and was approved in May 2007 by the European Commission.



ORENCIA in combination with methotrexate is indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have had an insufficient response or intolerance to other disease-modifying anti-rheumatic drugs including at least one tumour necrosis factor (TNF) inhibitor.


A reduction in the progression of joint damage and improvement of physical function have been demonstrated during combination treatment with ORENCIA and methotrexate.



The safety profile of ORENCIA has been studied through more than 10,000 patient-years of exposure and has demonstrated a consistent safety profile to 7 years.[2]



Medicinal products, including ORENCIA, which affect the immune system, may affect host defences against infections and malignancies. Serious infections, at least possibly related to treatment, were reported in 1.8% of patients with ORENCIA and in 1.0% of patients not treated by ORENCIA (receiving placebo). There is a need to evaluate and monitor patients regarding the risk of infection prior to and during treatment. In the placebo-controlled clinical trials, the frequency of malignancies with ORENCIA was 1.4% and with placebo 1.1%. These rates are similar to that observed in the general RA population.[6]



ORENCIA, like other biologics, is contraindicated in patients with severe and uncontrolled infections such as sepsis and opportunistic infections and in patients with hypersensitivity to the active substance or to any of the excipients. Allergic reactions have been reported uncommonly with ORENCIA in clinical trials, where patients were not required to be pretreated to prevent allergic reactions. In the case of any serious allergic/anaphylactic reaction, ORENCIA should be discontinued.



About Rheumatoid Arthritis



RA is a systemic, chronic, autoimmune disease characterised by inflammation in the lining of joints (or synovium), causing joint damage with chronic pain, stiffness and swelling. RA causes limited range of motion and decreased function as a result of affected joints losing their shape and alignment. RA may affect up to 7 million people in Europe.[7],[8]




References:


[1] Westhovens, R et al. Consistent Safety and Sustained Improvement in Disease Activity and Treatment Response Over 7 Years of Abatacept Treatment in Biologic-Na??ve Patients with RA. EULAR 2009, abstract no. FRI0108.


[2] Smitten, A et al. Descriptive Analysis of Serious Infections, Hospitalized Infections and Malignancies Over Time in the Abatacept Clinical Development Program: A Safety Update with >10,000 Person-Years of Exposure. EULAR 2008, abstract no. 1065.


[3] Kremer JM et al. Abatacept Demonstrates Consistent Safety and Sustained Improvements in Efficacy Through 5 Years of Treatment in Biologic-Na??ve Patients with RA. EULAR 2009, abstract no. FRI0263.


[4] Genant, HK el al. Abatacept Increases the Proportion of Patients who Remain Free From Structural Damage Progression Through 5 Years in Methotrexate Inadequate Responders with RA.EULAR 2009, abstract no. FRI0253.


[5] Kremer, JM et al. Treatment of Rheumatoid Arthritis by Selective Inhibition of T-Cell Activation with Fusion Protein CTLA4Ig. N. Engl. J. Med. 2003;349:1907-1915.


[6] Simon, T et al. Ann Rheum Dis 2006;65(Suppl II):489.


[7] United Nations. 2008 Revision Population Database. esa.un/unpp/ Accessed 14-05-09.


[8] Symons, D et al. The Global Burden of Rheumatoid Arthritis in the Year 2000. See here. Accessed 14-05-09.



Source
Bristol-Myers Squibb


View drug information on Orencia.

The Gerontological Society Of America Announces 2008 Hartford Faculty Scholars

Ten outstanding geriatric social work faculty members have been chosen as the newest inductees into the Hartford Faculty Scholars Program, a venture funded by the John A. Hartford Foundation, administered by The Gerontological Society of America, and directed by Dr. Barbara Berkman. The individuals who receive this distinction are provided with opportunities for professional development and $100,000 in funding over the next two years for research on topics related to improving health and care for older adults and their caregivers.



Now in its ninth year, the award aims to improve the well-being of older adults by increasing the number of adequately trained geriatric social workers. Listed below are the new faculty scholars and the primary topics of their research.



Richard Beaulaurier, PhD

Florida International University

School of Social Work

Research Focus: Older Latinos and HIV: Provider Perspectives



Victoria Rizzo, PhD

Columbia University

School of Social Work

Research Focus: A Social Work Care Coordination Program for Osteoarthritis: A Pilot Study



Banghwa Lee Casado, PhD

University of Maryland

School of Social Work

Research Focus: An Examination of the Caregiving Experience and Home and Community-Based Services Needs among Caregivers of Older Korean Americans



Louise Quijano, PhD

Colorado State University

School of Social Work

Research Focus: Vida Tranquila II: A Skills-Based Therapeutic Intervention for Older Latino Primary Care Patients with Generalized Anxiety Disorder



Rita Chou, PhD

University of South Carolina

College of Social Work

Research Focus: Job Satisfaction and Productive Aging: A Longitudinal Study of Older Workers Based on a Nationally Representative Sample



Sudershan Pasupuleti, PhD

University of Toledo

Social Work Department

Research Focus: Impact of Computer-Based Brain Fitness Program on Cognitive Functioning and Quality of Life of Older Adults in Public Dwellings



Kim Stansbury, PhD

Eastern Washington University

School of Social Work & Human Services

Research Focus: Attitudes and Knowledge of Older Adults toward Casinos and Disordered Gambling



Marilyn Luptak, PhD

University of Utah

College of Social Work

Research Focus: Caring for Older Adults with Depression: A Family Perspective



Angela Curl, PhD

University of Missouri

School of Social Work

Research Focus: The Impact of Retirement on Heart Problems: A Multilevel Dyadic Analysis of Longitudinal Secondary Data



Scott Wilks, PhD

Louisiana State University

School of Social Work

Research Focus: Examining an Appraisal Model of Burden, Coping, and Resilience: Differences among African American and Caucasian Alzheimer's Caregivers



Berkman, the Helen Rehr/Ruth Fizdale Professor at Columbia University's School of Social Work, works together with a national program committee involved in the selection of Scholars. This committee consists of David E. Biegel of Case Western Reserve University, Letha Chadiha of the University of Michigan, Namkee Choi of the University of Texas at Austin, Ruth Dunkle of the University of Michigan, Nancy R. Hooyman of the University of Washington, Amy Horowitz of the Jewish Home and Hospital Lifecare System, Rosalie A. Kane of the University of Minnesota, Philip McCallion of the State University of New York at Albany, and Victoria Raveis of Columbia University. Ad hoc members include James Lubben of Boston College and the Hartford Doctoral Fellows Program and Jack R. Sellers of the University of North Alabama.







The Gerontological Society of America is the nation's oldest and largest multidisciplinary organization devoted to research, education, and practice in the field of aging. The principal mission of the Society - and its 5,000+ members - is to advance the study of aging and disseminate information among scientists, decision makers, and the general public.



Source: Todd Kluss


The Gerontological Society of America

Blood Test Can Predict Rheumatoid Arthritis Before Symptoms Arise

Researchers from University Hospital in Umea, Sweden, have identified several cytokines, cytokine-related factors, and chemokines that increase significantly prior to rheumatoid arthritis (RA) disease onset. These findings confirm those of earlier studies which suggest that the risk of developing RA can be predicted and disease progression may be prevented. Complete findings of this study are published in the February issue of Arthritis & Rheumatism, a journal of the American College of Rheumatology.



Rheumatoid arthritis is a chronic autoimmune disease characterized by joint inflammation involving the synovial (lubricating fluid of the joints) tissue and eventually leading to destruction of cartilage and bone. The cause leading to disease development and progression is not completely understood, although various cells of the immune system and of synovial origin are suggested to be involved. Numerous cytokines are expressed and are functionally active in the synovial tissue once the disease has developed. Now a research team led by Solbritt Rantap?¤?¤-Dahlqvist, M.D. has found that several of these cytokine levels spike as much as several years prior to the development of arthritic symptoms.



An early and accurate diagnosis of RA is crucial. According to the American College of Rheumatology, RA can be difficult to diagnose because it may begin with only subtle symptoms, such as achy joints or early morning stiffness. Many diseases including lupus, osteoarthritis and fibromyalgia, especially early on, mimic the symptoms of RA making diagnosis more difficult. Studies have shown that people who receive early treatment for RA feel better sooner and more often, are more likely to lead an active life, and are less likely to experience the type of joint damage that leads to joint replacement.



To determine whether cytokines, cytokine-related factors, and chemokines are up-regulated prior to the development of RA, and which ones are involved, the team conducted a nested case-control study within the Medical Biobank of Northern Sweden. Blood samples were analyzed from 86 individuals before the appearance of symptoms of RA (pre-patients), from 69 of the pre-patients after the onset of RA, and from 256 matched control subjects (1:3 ratio). A consecutive time-dependent involvement of the immune system in disease development and progression was evaluated. The plasma levels of 30 cytokines, related factors, and chemokines were measured using a multiplex system. Individuals in whom RA subsequently developed were discriminated from control subjects mainly by the presence of Th1 cell-, Th2 cell-, and Treg cell-related cytokines, while chemokines, stromal cell-derived cytokines, and angiogenic-related markers separated patients after the development of RA from individuals before the onset of RA.



"We observed a clear relationship between cytokines related not only to Th1, Th2, and Treg cells but also to Th17 and the presence of anti-CCP antibodies, thereby supporting the concept that the immune system was already stimulated and disease was developing toward RA," explains Dr. Rantap?¤?¤-Dahlqvist. Researchers found that blood samples obtained from individuals had elevated concentrations of proinflammatory cytokines, cytokine-related factors, and chemokines, indicating immune system activation prior to any symptoms of joint involvement. "Our findings present an opportunity for better predicting the risk of developing RA and possibly preventing disease progression," concluded Dr. Rantap?¤?¤-Dahlqvist.



Article: "Up-Regulation of Cytokines and Chemokines Predates the Onset of Rheumatoid Arthritis." Heidi Kokkonen, Ingegerd S?¶derstr?¶m, Joacim Rockl?¶v, G?¶ran Hallmans, Kristina Lejon, and Solbritt Rantap?¤?¤-Dahlqvist. Arthritis & Rheumatism; Published Online: January 28, 2010 (DOI: 10.1002/art.27186); Print Issue Date: February 2010.



Source:
Dawn Peters

Wiley-Blackwell

New Online Resource For Patients With Severe Hip Osteoarthritis

DePuy Orthopaedics, Inc., announced an advancement in online education for the more than 200,000 Americans who undergo hip replacement each year.1 This extensive patient Web site, hipreplacement, provides hip pain patients with a broad range of resources from mobility assessment tools to surgical options and recovery information, as well as linking to an online discussion group for peer-to-peer support.


"While many sites offer information about osteoarthritis and hip replacement, hipreplacement takes this a step further by helping find information to sort through the decision making process," says Randy Kilburn, director of Hip Marketing at DePuy. "DePuy's goal is to educate, empower, and encourage patients to seek treatment by informing them about orthopaedic solutions and bringing them together with surgeons."


hipreplacement also features extensive information about hip pain treatment options, including the latest advances in hip surgery such as computer-assisted surgery and the Anterior Approach; education about what to expect before, during and after hip replacement surgery; testimonials from patients who have had hip replacement; and an orthopaedic surgeon locator.


About Hip Replacement


The demand for hip replacement is growing rapidly. It is estimated that the number of primary total hip replacements will increase by 174 percent to 572,000 in 2030. The demand for hip revision procedures is projected to double by the year 2026. Overall, total hip revisions are projected to grow by 137 percent between 2005 and 2030.2 This is due in part to the growing number of Baby Boomers with osteoarthritis and the rise in obesity among the population.3


The performance of hip replacements depends on age, weight, activity level, and other factors. There are potential risks and recovery takes time. People with conditions limiting rehabilitation should not have this surgery. Only an orthopaedic surgeon can tell if hip replacement is right for a patient.


To learn more, please visit hipreplacement.


About DePuy Orthopaedics, Inc.


DePuy Orthopaedics, Inc., a Johnson & Johnson company, is advancing the standard of orthopaedic patient care, with a focused commitment to help surgeons achieve excellence in surgical practice. Countless surgeons worldwide rely upon DePuy Orthopaedics every day in their treatment of patients. The company designs, manufactures and distributes orthopaedic devices and supplies including hip, knee, extremity, trauma, cement, orthobiologics, and operating room products. As a global leader in joint replacement products, DePuy Orthopaedics is committed to Restoring the Joy of Motion™ for patients whose mobility is restricted by severe osteoarthritis or other debilitating injury.


References:


1 Data on file at DePuy Orthopaedics, Inc.


2 "Projections of Primary and Revision Hip and Knee Arthroplasty in the United States from 2005 to 2030." Steven Kurtz, Kevin Ong, Edmund Lau, Fionna Mowat and Michael Halpern. The Journal of Bone and Joint Surgery (American). July 2007;89:780-785.


3 "Total Knee and Hip Replacement Surgery Projections Show Meteoric Rise by 2030. Orthopaedic procedures set to continue gaining widespread acceptance as means to restore quality-of-life," American Academy of Orthopaedic Surgeons (AAOS) Web site: www6.aaos/news/Pemr/press_release.cfm?PRNumber=442. Accessed July 11, 2007.

Subclinical Markers Predict Relapse In Juvenile Idiopathic Arthritis Post Methotrexate Withdrawal

Elevated levels of the inflammatory biomarkers Myeloid Related Protein (MRP*) 8/14 predict an increased risk of relapse following withdrawal of methotrexate (MTX) therapy in children with juvenile idiopathic arthritis (JIA) who have achieved inactive disease status, according to a new study presented at PReS 2009, a joint congress with the 2009 Congress of the European League Against Rheumatism (EULAR) in Copenhagen, Denmark.



Effective treatment options are available to treat rheumatic diseases, many of which have the potential to induce remission, defined as absence of signs or symptoms of disease. While there is evidence-based advice regarding when to initiate therapy in rheumatic diseases, there is no specific guidance on the timing of treatment withdrawal once a state of remission on medication is achieved. While this holds true for many autoimmune disease (such as Rheumatoid Arthritis, Crohn's disease, Ulcerative Colitis, or Autoimmune Hepatitis), in the case of MTX therapy for JIA, a continuation of MTX for 12 to 24 months after induction of remission has been proposed by researchers.1



The risk of relapse in JIA patients, once MTX is discontinued, is approximately 50%.2 However, the results of this study have shown that continuing MTX therapy past the point of remission does not affect the risk of relapses after withdrawal of therapy. Clinical (disease subtype, duration or dosage of therapy, duration of MTX therapy) or standard laboratory tests (c-reactive protein and erythrocyte sedimentation rate as measurements of inflammation) could not differentiate between patients at-risk for relapse and those without this risk. However, MRP8/14 levels were significantly higher at MTX withdrawal in remission in those patients who subsequently developed relapses (715?±140 ng/ml) compared to patients with stable remission (400?±105 ng/ml; p=0.003).



Levels of MRP8/14 were especially high in patients with relapses occurring within 6 months, compared to 12 months. (955?±270 ng/ml; p< 0.001).



Professor Dirk Foell of the University of Muenster, Germany, who conducted the study, said: "Methotrexate is effective in children with JIA and can induce a status of inactive disease. This is the first controlled trial analyzing the necessary time of treatment continuation once remission is achieved in a rheumatic disease. Our study shows that patients with elevated levels of MRP 8/14 may specifically benefit from prolonged treatment and also that a longer duration of MTX therapy after achieving remission does not influence the risk of relapse on patients with JIA. The results of our research help to make the case for the tracking of levels of biomarkers as predictors of treatment responses in this unique patient population."



In the PRINTO** study, 364 JIA patients with inactive disease for at least 3 months were randomised to receive additional MTX for either 6 or 12 months. Serum sample analysis using ELISA (Enzyme-Linked Immunosorbent Assay) was conducted in 188 patients to track MRP8/14 levels at 3 month baseline, and again at either 6 or 12 months according to study protocol. Patients were followed-up for at least 12 months after MTX discontinuation.
















A log-rank analysis confirmed the differences in relapse rates between patients with MRP8/14 levels of 900ng/ml or above, compared to those with lower levels (p< 0.001). ROC (Receiver operating characteristics) analysis revealed a sensitivity of 50% and a specificity of 78% for predicting relapses at this cut-off (likelihood ratio for relapse 2.3), while the specificity was increased to 90% at a cut-off at 1400ng/ml (likelihood ratio 3.4).



At baseline, demographic and clinical characteristics were well balanced and all patients had inactive disease status. 59 (31%) had the JIA subtype of persistent oligoarthritis, 27 (14%) extended oligoarthritis, 64 (34%) polyarthritis RF-negative, 10 (5%) polyarthritis RF-positive, 12 (6%) systemic and 16 (9%) other JIA subtypes. Patients had previously been treated with MTX at a dose of 11.6?±2.8 mg/m2/week for 2.3?±2.1 years. The overall rate of flares was 92/188 (49%) patients.



JIA is the most common inflammatory autoimmune childhood disease, affecting approximately 1 in 1,000 children. Despite advances in diagnosis and treatment options, it remains a chronic condition for most affected children with a significant disease burden.



Notes:

*MRP 8 and 14 are pro-inflammatory damage associated molecular pattern (DAMP) molecules that play an important role in inflammatory and immunological responses. They have recently been identified as activators of Toll like receptor (TLR-4), a molecule that amplifies phagocyte activation (a type of white blood cell (leukocyte), that supports the immune system by neutralising or engulfing bacteria or other invading micro-organisms.


**PRINTO (Paediatric Rheumatology International Trials Organization) is an international not-for-profit research network that fosters, facilitates and co-ordinates international trials of children with rheumatic diseases.


Abstract number: THU0412


References:


1 Ravelli A, Viola S, Ramenghi B, Aramini L, Ruperto N, Martini A. Frequency of relapse after discontinuation of methotrexate therapy for clinical remission in juvenile rheumatoid arthritis. J Rheumatol 1995;22:1574-6].


2 Gottlieb BS, Keenan GF, Lu T, Ilowite NT. Discontinuation of methotrexate treatment in juvenile rheumatoid arthritis. Pediatrics 1997;100:994-7].



Source:
Rory Berrie


European League Against Rheumatism

Adolescents With Arthritis Need More Information When Transitioning To Adult Care

Helping adolescents with arthritis develop the skills and secure resources to assure that their health care needs are met as they transition to adulthood is an important issue in the U.S. In general, the frequency of which young people with special health care needs receive transition services is low and, to date, no studies have examined this frequency.



A new study examined the extent to which adolescents with arthritis receive transition services and compared these rates to youth with other special care health needs. The study was published in the January issue of Arthritis Care & Research (www3.interscience.wiley/journal/77005015/home).



Led by Peter Scal of the University of Minnesota, researchers used information from the 2005-2006 National Survey of Children with Special Health Care Needs to identify adolescents aged 12 to 17 who had arthritis and to assess responses to questions about the transition to adulthood and adult-oriented health care.



The results showed that nearly three-quarters of adolescents with arthritis were encouraged to take responsibility for their health care needs and about half discussed how their needs might change when they became an adult. Only one in five, however, received counseling about the need to transfer to adult-oriented physicians and how to obtain health insurance as an adult. These results were similar to young people with special health care needs nationally, but lag behind those with diabetes.



"Health care transition is a complex set of tasks that are embedded within a complex developmental period and a complex heath care system," the authors note. "It is not surprising, then, than the development and evaluation of services to facilitate health care transition has been slow." However, a systematic approach to this problem can show results.



In the UK, for example, the British Society of Paediatric and Adolescent Rheumatology has developed a comprehensive health care transition program for youth with arthritis that appears to have a positive impact.



In the U.S., there seems to be much room for improvement is assisting adolescents with arthritis in achieving a successful health care transition into adulthood. "More research is needed to understand youth's perspectives regarding their health care transition needs that should include items related specifically to health care transition, as well as how health care transition needs intersect with social, educational, and vocational concerns," the authors conclude.







Article: "Preparing for Adulthood: Health Care Transition Counseling for Youth with Arthritis," Peter Scal, Keith Horvath, Ann Garwick, Arthritis & Rheumatism (Arthritis Care & Research), January 2009; 61:1; pp. 52-57.



Source: Sean Wagner


Wiley-Blackwell

Centocor Ortho Biotech Inc. Submits Application To FDA Seeking To Expand SIMPONI(R) Label In Treatment Of Rheumatoid Arthritis

Centocor Ortho Biotech Inc. announced today that it has submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) seeking to expand the SIMPONI® (golimumab) physician label to include inhibiting the progression of structural damage, inducing major clinical response (MCR) and maintenance of reducing signs and symptoms and improving physical function in the treatment of moderately to severely active rheumatoid arthritis (RA).


SIMPONI received U.S. FDA approval in April 2009 and became the first once-monthly anti-tumor necrosis factor (TNF)-alpha therapy approved for the treatment of adults with moderately to severely active RA, active psoriatic arthritis and active ankylosing spondylitis. For the RA indication, SIMPONI is given in combination with the drug methotrexate.


The sBLA is supported by long-term efficacy and safety data from three pivotal Phase 3 registration trials of three diverse moderately to severely active RA patient populations - patients na??ve to methotrexate, patients who had an inadequate response to methotrexate and patients previously treated with one or more anti-tumor necrosis factor (TNF)-alpha agents.


"This application represents yet another milestone for the SIMPONI clinical development program," said Jerome A. Boscia, M.D., senior vice president, Clinical R&D, Centocor Research & Development, Inc. "We look forward to collaborating with the FDA in reviewing the data from our Phase 3 registration trials that support the efficacy of SIMPONI in inhibiting the progression of structural damage in patients with moderately to severely active rheumatoid arthritis."


About Rheumatoid Arthritis


RA is a chronic inflammatory condition that is often characterized by symptoms that include pain, stiffness and inflammation, and in some cases, joint destruction and disability. More than one million Americans are living with RA, the majority of whom are women. The Arthritis Foundation estimates that approximately 1.3 million people in the United States are affected by RA.


About SIMPONI


SIMPONI is a human monoclonal antibody that targets and neutralizes excess TNF-alpha, a protein that when overproduced in the body due to chronic inflammatory diseases can cause inflammation and damage to bones, cartilage and tissue. A once-monthly subcutaneous anti-TNF-alpha therapy with marketing authorizations in the Unites States, Europe and Canada, SIMPONI is approved for the treatment of moderately to severely active RA in combination with methotrexate, active psoriatic arthritis and active ankylosing spondylitis. SIMPONI is available either through the SIMPONI SmartJect™ autoinjector or a prefilled syringe. For more information about SIMPONI, visit SIMPONI.















Centocor Ortho Biotech Inc. discovered and developed SIMPONI and has exclusive marketing rights to the product in the United States.


Important Safety Information


SIMPONI® (golimumab) is a prescription medicine. SIMPONI® can lower your ability to fight infections. There are reports of serious infections caused by bacteria, fungi, or viruses that have spread throughout the body, including tuberculosis (TB) and histoplasmosis. Some of these infections have been fatal. Your doctor will test you for TB before starting SIMPONI® and will monitor you for signs of TB during treatment. Tell your doctor if you have been in close contact with people with TB. Tell your doctor if you have been in a region (such as the Ohio and Mississippi River Valleys and the Southwest) where certain fungal infections like histoplasmosis or coccidioidomycosis are common.


You should not start SIMPONI® if you have any kind of infection. Tell your doctor if you are prone to or have a history of infections or have diabetes, HIV or a weak immune system. You should also tell your doctor if you are currently being treated for an infection or if you have or develop any signs of an infection such as:


- fever, sweat, or chills

- muscle aches

- cough

- shortness of breath

- blood in phlegm

- weight loss

- warm, red, or painful skin or sores on your body

- diarrhea or stomach pain

- burning when you urinate or urinate more than normal

- feel very tired


Unusual cancers have been reported in children and teenage patients taking TNF-blocker medicines. For children and adults taking TNF blockers, including SIMPONI®, the chances for getting lymphoma or other cancers may increase. You should tell your doctor if you have had or develop lymphoma or other cancers.


Tell your doctor about all the medications you take including ORENCIA (abatacept), KINERET (anakinra), RITUXAN (rituximab) or another TNF blocker, or if you are scheduled to or recently received a vaccine. People taking SIMPONI® should not receive live vaccines.


Reactivation of hepatitis B virus has been reported in patients who are carriers of this virus and are taking TNF-blocker medicines, such as SIMPONI®. Some of these cases have been fatal. Your doctor may do blood tests before and after you start treatment with SIMPONI®. Tell your doctor if you know or think you may be a carrier of hepatitis B virus or if you experience signs of hepatitis B infection, such as:


- feel very tired

- skin or eyes look yellow

- little or no appetite

- vomiting

- muscle aches

- dark urine

- clay-colored bowel movements

-fevers

- chills

- stomach discomfort

- skin rash


Heart failure can occur or get worse in people who use TNF blockers, including SIMPONI®. Your doctor will closely monitor you if you have heart failure. Tell your doctor right away if you get new or worsening symptoms of heart failure like shortness of breath or swelling of your lower legs or feet.


Rarely, people using TNF blockers, including SIMPONI®, can have nervous system problems such as multiple sclerosis. Tell your doctor right away if you have symptoms like vision changes, weakness in your arms or legs, or numbness or tingling in any part of your body.


Liver problems can happen in people using TNF blockers. Contact your doctor immediately if you develop symptoms such as feeling very tired, skin or eyes look yellow, poor appetite or vomiting, or pain on the right side of your stomach.


Low blood counts have been seen with people using TNF blockers, including SIMPONI®. If this occurs, your body may not make enough blood cells to help fight infections or help stop bleeding. Your doctor will check your blood counts before and during treatment. Tell your doctor if you have signs such as fever, bruising, bleeding easily, or paleness.


Rarely, people using TNF blockers have developed lupus-like symptoms. Tell your doctor if you have any symptoms such as a rash on your cheeks or other parts of the body, sensitivity to the sun, new joint or muscle pain, becoming very tired, chest pain or shortness of breath, swelling of the feet, ankles, and/or legs.


New or worse psoriasis symptoms may occur. Tell your doctor if you develop red scaly patches or raised bumps that are filled with pus.


Tell your doctor if you are allergic to rubber or latex. The needle cover contains dry natural rubber.


Tell your doctor if you have any symptoms of an allergic reaction while taking SIMPONI® such as hives, swollen face, breathing trouble, chest pain.


Common side effects of SIMPONI® include: upper respiratory tract infection, nausea, abnormal liver tests, skin reaction at site of injection, high blood pressure, flu, and cold sores.


Please read the Medication Guide for SIMPONI® and discuss any questions you have with your doctor.


Source:

Centocor Ortho Biotech Inc.


View drug information on Kineret; Orencia; Rituxan.