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  • Publication # 14-RA005

Start methotrexate as first-line therapy for patients with early, poor-prognosis rheumatoid arthritis

Chronic Disease

Most evidence-based guidelines call for methotrexate (MTX) by itself as first-line therapy for rheumatoid arthritis. Recent trials, however, suggest that combination therapy may be better. 

Yet, a new study concludes that methotrexate should be first-line therapy for patients with early rheumatoid arthritis even if they have poor prognostic features. The researchers compared the results of initial MTX monotherapy with the option to step up to combination therapy with immediate initial combination therapy in RA patients with an early poor prognosis. The results validated starting MTX monotherapy in these patients, since 28 percent did not need a step up to combination therapy, and those who did fared as well as those started on combinations from the outset. 

Image: A patient with rheumatoid arthritis. A total of 755 patients with early, poor-prognosis RA participated in the Treatment of Early Rheumatoid Arthritis trial. Each was randomized to receive MTX therapy alone or 1 of 2 different combination therapies: MTX and etanercept or MTX, sulfasalazine, and hydroxychloroquine. At 24 weeks, MTX monotherapy patients could be stepped up to combination therapy if their disease was still active. 

From week 48 to 102, disease activity scores, pain assessment, and radiographic outcomes in patients started on MTX monotherapy and then stepped up to combination therapy were indistinguishable from those in patients who immediately started on combination therapy. 

Within the MTX group, 28 percent did not require any step up to combination therapy. Monotherapy patients had less radiographic progression at week 102 than did patients receiving immediate combination therapy. The researchers point out the cost-saving measures associated with starting MTX alone. In addition, these results challenge recommendations by the American College of Rheumatology, which calls for this patient population to receive combination therapy at initial diagnosis. These new findings will need to be considered when the guidelines are revised. The study was supported in part by AHRQ (HS18517). 

See "Validation of the methotrexate-first strategy in patients with early, poor-prognosis rheumatoid arthritis," by James R. O'Dell, M.D., Jeffrey R. Curtis, M.D., M.P.H., Ted R. Mikuls, M.D., M.S.P.H., and others in Arthritis & Rheumatism 65(8), pp. 1985-1994, 2013.


Page last reviewed March 2014
Internet Citation: Start methotrexate as first-line therapy for patients with early, poor-prognosis rheumatoid arthritis: Chronic Disease. March 2014. Agency for Healthcare Research and Quality, Rockville, MD.


The information on this page is archived and provided for reference purposes only.


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