A trial of etanercept, a recombinant tumor necrosis factor receptor : Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate

Background Patients treated with methotrexate for rheumatoid arthritis ofte n improve but continue to have active disease. This study was undertaken to determine whether the addition of etanercept, a soluble tumor necrosis fac tor receptor (p75):Fc fusion protein (TNFR:Fc), to methotrexate therapy wou ld provide additional benefit to patients who had persistent rheumatoid art hritis despite receiving methotrexate. Methods In a 24-week, double-blind trial, we randomly assigned 89 patients with persistently active rheumatoid arthritis despite at least 6 months of methotrexate therapy at a stable dose of 15 to 25 mg per week (or as low as 10 mg per week for patients unable to tolerate higher doses) to receive ei ther etanercept (25 mg) or placebo subcutaneously twice weekly while contin uing to receive methotrexate. The primary measure of clinical response was the American College of Rheumatology criteria for a 20 percent improvement in measures of disease activity (ACR 20) at 24 weeks. Results The addition of etanercept to methotrexate therapy resulted in rapi d and sustained improvement. At 24 weeks, 71 percent of the patients receiv ing etanercept plus methotrexate and 27 percent of those receiving placebo plus methotrexate met the ACR 20 criteria (P < 0.001); 39 percent of the pa tients receiving etanercept plus methotrexate and 3 percent of those receiv ing placebo plus methotrexate met the ACR 50 criteria (for a 50 percent imp rovement) (P < 0.001). Patients receiving etanercept plus methotrexate had significantly better outcomes according to all measures of disease activity . The only adverse events associated with etanercept were mild injection-si te reactions, and no patient withdrew from the study because of adverse eve nts associated with etanercept. Conclusions In patients with persistently active rheumatoid arthritis, the combination of etanercept and methotrexate was safe and well tolerated and provided significantly greater clinical benefit than methotrexate alone. (N Engl J Med 1999;340:253-9,) (C) 1999, Massachusetts Medical Society.