Rheumatoid arthritis is the most common chronic autoimmune disease that affects the joints. RA has the potential for joint damage and deformity, with loss of function. The cause of RA is unknown. It affects people of all ages, and women more commonly than men. RA causes pain, stiffness and swelling, generally in multiple joints. RA may affect any joint, but the small joints in the hands and feet are most frequently involved.
Anti-tumor necrosis factor (commonly called anti-TNF) drugs are a class of drugs that are used worldwide to treat inflammatory conditions such as RA. These drugs are often able to reduce inflammation and stop disease progression, but one-third of patients do not find success when taking them to treat RA. When this happens, rheumatologists often consider one of two strategies: trying a second anti-TNF drug or switching to a non-TNF-targeted biologic. While these two strategies have been compared by observation, researchers from France recently put them to the test in a 48-week randomized study of 292 people.
“These two strategies (a non-TNF biologic or a second anti-TNF) have been compared in scarce observational studies, in patients who did not respond to their first anti-TNF,” says lead investigator in the study, Jacques-Eric Gottenberg, MD, PhD; National Reference Center For Systemic Autoimmune Diseases; Department of Rheumatology, Strasbourg University Hospital, France. “However, no randomized controlled trial has compared the effectiveness of a non-TNF-targeted biologic and a second anti-TNF drug in these patients. Recently, the European League Against Rheumatism recommendations acknowledged the absence of evidence to guide the choice of a second biologic in TNF-IR patients, which further confirmed the need for studies like this one.”Participants in the study were randomly assigned to either receive a non-TNF-targeted biologic or a second anti-TNF when it was established that the first anti-TNF was not working. Each participant’s physician was able to make the choice of the biologic within each randomized group (i.e. adalimumab, certolizumab, etanercept or infliximab in the 2d anti-TNF group; abatacept, rituximab or tocilizumab in the non-TNF targeted biologic group). Dr. Gottenberg’s team followed up with the participants at three, six and 12 months to determine how they were reacting to their new treatment strategies.
At three months, 64.2 percent the participants on the non-TNF-targeted biologics and 47.8 percent of the participants on a second anti-TNF achieved a good or moderate response (based on EULAR criteria). At six months, this increased to 69.7 and 52.1 percent; and at 12 months, they dropped to 60 and 43.2 percent. The researchers also looked at disease activity scores and noted that they were lower for participants on the non-TNF-targeted biologic than those who began a second anti-TNF. Among the groups, 40.8 percent and 23.5 percent achieved low disease activity, respectively. And, 26.9 and 13.6 percent achieved remission.
“This study demonstrated a better effectiveness of a non-TNF-targeted biologic than a second anti-TNF agent for patients who did not respond to their first anti-TNF. This superiority was consistent throughout the study period and across numerous outcome criteria in a setting nearing common practice, with no significant difference in the safety two treatment strategies evaluated,” Dr. Gottenberg explains. “However, at least 40 percent of patients failed to respond to their second-line biologic, which emphasizes the unmet need to continue to increase the number of treatment options and develop personalized medicine for people with RA.“
Dr. Gottenberg’s team embarked on a second study that looked at patients to specifically see if the presence of anti-drug antibodies would have been helpful in choosing a second biologic.
“Sometimes a person’s immune system can fight against a drug being used to treat a disease. This causes the body to create anti-drug antibodies, which may render the drug useless and may even cause side effects. We wanted to see if these antibodies were present in people who weren’t having success with anti-TNF drugs because we believe this knowledge could help a rheumatologist make a better choice for the second treatment strategy,” Dr. Gottenberg says of the second study.
In this study, Dr. Gottenberg’s team retrospectively looked at anti-drug antibodies in 278 patients (pulled from the participants of the first study). At the beginning of the study, anti-drug antibodies could not be detected in 19 patients because the residual concentration of their first anti-TNF prevented the detection of these antibodies; no anti-drug antibodies were detected in 227 patients; and 32 patients did have the presence of anti-drug antibodies. In the 32 patients who did have the presence of anti-drug antibodies, blood levels of the first anti-TNF were very low or undetectable, which might be related to the binding of the first anti-TNF to anti-drug antibodies.
Dr. Gottenberg further explains, “In such a subpopulation of patients with anti-drug antibodies and converse to the overall results of the trial, the effectiveness of a second anti-TNF was not significantly different from a non-TNF targeted biologic. Assessing the presence of anti-drug antibodies might therefore help to choose a second biologic after a first anti-TNF doesn’t work. Meaning, the absence of anti-drug antibodies might indicate that RA is not TNF-driven in a given patient, and the best choice might be to change the treatment plan and use a non-TNF; whereas, in the presence of anti-drug antibodies, the choice of a second anti-TNF might be as successful as a non-TNF.”
Dr. Gottenberg says additional prospective studies evaluating the benefit of assessing anti-drug antibodies in order to guide the choice of a second biologic are needed and eagerly awaited.
About the American College of RheumatologyHeadquartered in Atlanta, Ga., the American College of Rheumatology is an international medical society representing over 9,400 rheumatologists and rheumatology health professionals with a mission to Advance Rheumatology! In doing so, the ACR offers education, research, advocacy and practice management support to help its members continue their innovative work and provide quality patient care. Rheumatologists are experts in the diagnosis, management and treatment of more than 100 different types of arthritis and rheumatic diseases. For more information, visit www.rheumatology.org.
About the ACR/ARHP Annual MeetingThe ACR/ARHP Annual Meeting is the premier meeting in rheumatology. For more information about the meeting, visit www.acrannualmeeting.org/ or join the conversation on Twitter by using the official #ACR15 hashtag.
ACR Abstracts 3113 & 3110 www.acrabstracts.org/
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