Newswise — ATLANTA – The American College of Rheumatology Research and Education Foundation today announced it has committed six million dollars to fund two clinical trials focused on rheumatoid arthritis. The first trial will explore stopping anti-TNF agents in disease remission, and the second will look at the potentially deadly cardiovascular risks associated with RA.
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 other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.
“These are the largest grants the REF has funded to date,” says REF President and Rheumatologist, David Daikh, MD, PhD. “Clinical trials are often funded through private sources or the National Institutes of Health – making the REF’s first foray into clinical trials especially important to the rheumatology community and to rheumatology patients. We’ve opened the door to more funding in this critical area of research.”
Is it Safe to Stop Anti-TNF Agents?
The first clinical trial funded by the REF will attempt to determine if people with RA who take anti-tumor necrosis factor agents – such as etanercept, adalimumab and infliximab – can maintain remission without that therapy.
“Many people with RA who take anti-TNF agents combined with methotrexate show significant improvement in joint pain and stiffness and often achieve clinical remission,” explains lead investigator Arthur Weinstein, MD, FACP, FRCP, MACR; professor of medicine at Georgetown University Medical Center and chief of rheumatology at MedStar Washington Hospital Center. “However, these medications are expensive, can lead to a higher frequency of infections, and may have other side effects.”
The trial will examine people with RA in clinical remission for at least six months on standard RA therapy (which includes anti-TNFs). The participants will continue to either receive their current medication or a placebo (without the anti-TNF). Participants and rheumatologists in the trial will not know which is being administered. Twice as many subjects will receive placebo as will remain on their anti-TNF drug. Standard treatment will be continued and patients will be closely followed for a recurrence of active RA for 48 weeks.
To predict which participants will experience an RA flare and which will remain in remission, researchers will conduct clinical examinations, joint X-rays, magnetic resonance imaging (commonly called MRI) of the hands, joint ultrasounds and scientific studies of the blood immune system.
“The trial will provide people with RA and practicing rheumatologists knowledge about successfully stopping anti-TNF agents and which RA patients may be effectively withdrawn on the basis of their clinical features, imaging results or blood immunology. In addition to providing this new information about stopping anti-TNF therapy in RA, this study — done in collaboration with the National Institute of Arthritis, Musculoskeletal and Skin Diseases — could become a model for future studies that answer important clinical questions about RA and other rheumatic diseases,” explains Dr. Weinstein.
Can Biologics Lessen The Risk Of Deadly Heart Disease Risk?
The second clinical trial examines if biologic medications, such as adalimumab, can lessen cardiovascular risks in people with RA. More specifically, the trial is the first study to determine whether accelerated treatment of well-controlled RA can reduce heart disease.
“Chronic inflammation is largely responsible for the increased risk of cardiovascular disease and higher death rates experienced by people with rheumatoid arthritis,” says co-investigator Jonathan Graf, MD; rheumatologist and assistant professor of medicine at the University of California, San Francisco. “Although inflammation is most prominent in joints, it can persist elsewhere in the body – even when you can’t see it in the joints. Current goals of RA treatment focus on controlling joint symptoms rather than mitigating cardiovascular risk. Biologic medications effectively treat joint symptoms while reducing levels of inflammation. We hope to learn if these therapies can also address cardiovascular risks and whether treating patients with low disease activity reduces cardiovascular threats.”
Throughout the trial, 60 participants with minimal symptoms on standard non-biologic therapy will be studied. Participants will receive six months of either adalimumab or placebo. In addition to standard treatment, patients will be evaluated for improvement in cardiovascular disease risk with a variety of tests that measure blood flow and function. Ultrasound will be used to measure artery dilation in the arm after standard blood pressure cuff testing. Lastly, researchers will assess change in cardiovascular risk by switching control groups – patients who previously received placebo will be switched to adalimumab and vice-versa.
“Because we have seen elevated levels of inflammation in people with RA who have mild inflammation in their joints, we expect there to be a significant improvement in cardiovascular disease risk when those patients are treated with adalimumab,” says co-investigator Peter Ganz, MD; division chief of cardiology at the University of California, San Francisco.
To initiate the clinical trials, the REF accepted proposals from researchers with interests in rheumatoid arthritis. The REF did not require certain topics to be covered by the trials; therefore, the researchers could propose studies within any area of RA research. The proposals were then reviewed by a peer review committee of the top researchers in rheumatoid arthritis, and the REF awarded Dr. Weinstein’s team and Drs. Graf and Ganz’s team the trials.
“The REF is leading a new era of rheumatology research that focuses on finding medical breakthroughs and cures, and these trials are a symbol of that,” says Dr. Daikh. “This year — in addition to these grants — the REF is funding over $12 million in career development awards and disease-targeted research grants to address the growing demand for patient care today while advancing the course of research that will yield tomorrow’s cures,” he says of the Foundation’s current work.
Visit the REF website at www.rheumatology.org/ref/stories/within_our_reach.asp#novel to learn more about these novel clinical trials.
The ACR Research and Education Foundation was established in 1985 as a 501c3 organization with a mission of advancing research and training to improve the health of people with rheumatic diseases. Building on more than 25 years of success, the Foundation works in collaboration with the American College of Rheumatology to lead the effort to ensure that rheumatology keeps pace with its rapidly growing challenges by cultivating the physicians, treatments and cures needed to care for those whose lives are touched by rheumatic disease. On average, 90 cents of every dollar donated to the Foundation is used to fund rheumatology training and development, and targeted research programs to advance treatment and find cures in the rheumatic diseases. For more information, visit www.rheumatology.org/foundation.