MTX Fails in RA. What Next? Reviewers Respond

January 7, 2015

For treating rheumatoid arthritis not responsive to methotrexate, DMARD combinations beat monotherapy but at greater risk, a summary of recent evidence observes. In another, reviewers disagree about triple therapy.

Abramowicz M. Drugs for Rheumatoid Arthritis.The Medical Letter on Drugs and Therapeutics, 2014;56(1458):127 December 22, 2014

Clinical Trials versus Real Life. More@MedLetter, December 8, 2014

ACP Journal Club Review: bDMARDs plus conventional synthetic DMARDs have greater efficacy than either alone in RA. Annals of Internal Medicine. 2014;161(12):JC8. doi:10.7326/0003-4819-161-12-201412160-02008

ACP Journal Club Review: bDMARDs are linked to increased risk for infection compared with conventional synthetic DMARDs in RA. Annals of Internal Medicine. 2014;161(12):JC9. doi:10.7326/0003-4819-161-12-201412160-02009 16 December 2014

What to do for rheumatoid arthritis (RA) after methotrexate failure? An effort to weigh in reveals a split among the experts.

A review in The Medical Letter summarizes disease-modifying anti-rheumatic drugs (DMARDs) and biological agents, including tumor necrosis factor (TNF) inhibitors and others. The summaries also address the monthly cost of each drug.

In a related blog, MedLetter editor-in-chief Mark Abramowicz MD recounts a controversy that arose during the editorial process.

In short, one expert asked to excludefrom the review a study published in the New England Journal of Medicine, saying the results were “not so.” That study concluded that, for patients unresponsive to methotrexate, "triple therapy" (adding hydroxychloroquine and sulfasalazine) was non-inferior to adding etanercept.

Another reviewer stated that the NEJM study results did not match his clinical experience, but felt the data were still valid. MedLetter chose to include the study results in the review.

Meanwhile, the American College of Physicians' Journal Club features two systematic reviews supporting EULAR recommendations for the management of rheumatoid arthritis (RA).  These conclude that combination therapy, including a biologic, is more effective than monotherapy with either conventional or biologic disease-modifying antirheumatic drugs (DMARDs), but that the combination carries a greater risk for serious infection or tuberculosis.

A commentary published alongside the reviews holds that biologics are an option for refractory disease, but notes that conventional triple therapy has similar results in the long term (citing a different study, this one from Europe).

Ami Schattner MD, from Hebrew University and Hadassah in Jerusalem, also notes in the commentary that that results from randomized trials may not be readily reproduced in clinical settings, that longer outcome studies are needed, and that bDMARDs are expensive and can be inconvenient to administer.

The reviews summarized by the ACP Journal Club excluded intra-articular corticosteroid injections from consideration. The Medical Letter review recommends them.