What to Add When Methotrexate Fails in Rheumatoid Arthritis Patients

Allan S. Brett, MD

Adding sulfasalazine plus hydroxychloroquine was noninferior to adding etanercept.

In methotrexate-treated patients with rheumatoid arthritis (RA), how does the addition of a biologic agent compare with addition of two conventional nonbiologic agents? This question was addressed in a double-blind, placebo-controlled, randomized trial that involved 353 RA patients who had received 15 to 25 mg of methotrexate weekly for at least 12 weeks and who required additional treatment.

While continuing methotrexate, patients received either sulfasalazine plus hydroxychloroquine (“triple therapy”) or the tumor necrosis factor (TNF) inhibitor etanercept (Enbrel). The primary endpoint was improvement in the DAS28, a composite index that includes both objective and subjective measures of disease activity. With blinding maintained, patients with inadequate responses were permitted to cross over to the other treatment at 24 weeks; 27% of patients in each group did so.

At 48 weeks, mean DAS28 improvement in the group initially randomized to triple therapy was statistically noninferior to DAS28 improvement in the initial methotrexate-etanercept group. Radiographic progression and frequency of serious adverse events were similar in the two groups.

Citation(s):

O'Dell JR et al. Therapies for active rheumatoid arthritis after methotrexate failure. N Engl J Med 2013 Jun 11; [e-pub ahead of print].

Bathon JM and McMahon DJ. Making rational treatment decisions in rheumatoid arthritis when methotrexate fails. N Engl J Med 2013 Jun 11; [e-pub ahead of print].