Predicting Who Will and Won’t Find Relief
Biologic drugs that inhibit tumor necrosis factor-α (TNF) – adalimumab (Humira), etanercept (Enbrel) and infliximab (Remicade) – have revolutionized the treatment of rheumatoid arthritis (RA). For many people, these medications significantly reduce the signs and symptoms of RA and some even go into remission. However, as many as 40 percent of clinical trial participants did not reach or sustain 20 percent improvement in their disease. In practice, people not getting adequate relief from one TNF inhibitor will often switch to a traditional disease-modifying antirheumatic drug (DMARD) or another biologic therapy. But right now, doctors don’t know who will benefit from the therapy and who will not; it’s a matter of trial and error.
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What Problem Was Studied?
Currently, physicians decide which medication to give a patient based on toxicity profiles, cost and patient and physician preference. Using the Arthritis Foundation’s Engalitcheff Arthritis Outcomes Initiative grant – in combination with other grants – scientists from Brigham and Women’s Hospital, Harvard Medical School in Boston and The University of Texas Health Science Center at Houston decided to find evidence that will help physicians make a more informed decision.
What Was Done in the Study?
The team – led by Sandeep K. Agarwal, MD, PhD and including Arthritis Foundation-funded researchers Michael E. Weinblatt, MD, and Daniel H. Solomon, MD, MPH – is seeking to identify which RA patients are not only likely to respond to but are also able to continue treatment with TNF inhibitors. In this particular study, they identified common clinical traits among people with RA who ended up going off their TNF drugs. Clinical data were collected, as was information about which medications the participants took and for how long.
What Were the Study Results?
Of the 922 people with RA in the Brigham Rheumatoid Arthritis Sequential Study, 503 reported that they received a TNF inhibitor: 304 were on etanercept, 71 on infliximab and 128 on adalimumab. Of the 503 taking a TNF inhibitor, 210 discontinued its use during the study.
Analysis of the data revealed that prior use of one TNF inhibitor was associated with a higher risk of discontinuing another. Taking methotrexate while taking the TNF inhibitor was associated with a higher rate of discontinuation as well. Higher disease activity scores and physician assessment scores six months before discontinuation were also associated with stopping a TNF inhibitor.
Predictors of staying on the TNF therapy were longer disease duration, prior use of a traditional DMARD and long-term methotrexate use.
What Does This Mean for People With RA?
The authors muse that perhaps people who do not respond to one TNF inhibitor may have a disease subtype that is not dependent on that particular chemical mediator. Other biologic response modifiers currently available include abatacept (Orencia), which blocks a particular chemical that triggers the overproduction of T cells; anakinra (Kineret), which inhibits production of interleukin-1; and rituximab (Rituxan), which stops the activation of B cells. The research team says, “Additional studies will be helpful to determine if patients who fail a single TNF inhibitor due to lack of efficacy are less likely to respond to a subsequent TNF inhibitor compared to a biologic response modifier targeting other molecular pathways, such as the pathways blocked by rituximab or abatacept.”
Dr. Agarwal adds, “Extending our understanding of the biological mechanisms as well as social influences underlying discontinuation of TNF inhibitors is essential so that we can develop clinical models to predict which antirheumatic therapeutic regimen will be of greatest benefit to patients with RA.”
Agarwal SK, Glass RJ, Shadick NA, et al. Predictors of discontinuation of tumor necrosis factor inhibitors in patients with rheumatoid arthritis. J Rheumatol 2008; e-pub ahead of print July 15.