Which Biologic Therapy Works Best for Rheumatoid Arthritis? Comparative Effectiveness Reviews Do Not Offer Firm Conclusions

Reports from the United States and Europe reference the lack of long-term effectiveness studies and the lack of comparative effectiveness studies as challenges in determining the most appropriate initial biologic disease-modifying antirheumatic drug (DMARD) treatment for patients with rheumatoid arthritis.

Various products are available for treatment of rheumatoid arthritis (RA), including corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and medications known as disease-modifying antirheumatic drugs (DMARDs). In May 2013, the Agency for Healthcare Research and Quality (AHRQ) published an update to a comparative effectiveness review for therapies available for RA.

To evaluate the comparative efficacy of treatments, investigators at the AHRQ used data from any trial with at least 100 participants. Investigators also used data from retrospective studies and metaanalyses. Among injectable biologic DMARD therapies, only abatacaept and infliximab have been directly compared in a head-to-head trial, with no differences in effectiveness detected.

Despite the lack of firm comparative conclusions from studies, investigators report that biologic DMARDs are more likely to reduce symptoms of RA by the American College of Rheumatology (ACR) criteria than traditional oral therapies.

Results of a network metaanalysis support similar overall tolerability ratings between oral and biologic therapies, but short-term adverse events were more common with use of injectable, biologic DMARDs than with oral therapies. Of biologic DMARDs, etanercept may be more tolerable than other therapies since the rate of withdrawal due to adverse events was lower with etanercept than with other biologic DMARDs. Withdrawal of therapy due to a lack of efficacy is less likely with certolizumab pegol than with adalimumab, anakinra, or infliximab.

In August 2013, the Institute for Quality and Efficiency in Health Care (IQWIG) in Europe published a similar analysis. Like the AHRQ report, the IQWIG recommends use of 1 of the 9 available biologics as second-line therapy for RA. Of these 9 therapies, the IQWIG report mentions 5 treatments with the strongest evidence for efficacy: abatacept, adalimumab, certolizumab pegol, golimumab, and tocilizumab.

Investigators in the United States and Europe found some weak evidence for differences in the efficacy of biologic DMARDs, but these differences are not sufficient to support prioritizing one biologic DMARD before any other in a treatment algorithm.

Equivocal evidence has been a challenge for rheumatologists in the past. Methotrexate, sulfasalazine, and leflunomide are oral DMARDs for RA that have been available for many years. Even after direct comparison of products in clinical trials, investigators did not find clinically significant differences between therapies. Oral DMARDs continue to be selected based on clinical experience. If the results of network metaanalyses are any indication, direct comparisons of injectable, biologic DMARDs for RA in head-to-head trials may yield similar equivocal results in terms of comparative efficacy.