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TNF Inhibitors for Rheumatoid Arthritis

Two inhibitors of tumor necrosis factor (TNF) -- etanercept (Enbrel), which binds to TNF, and infliximab (Remicade), a monoclonal antibody against TNF -- now are available for treatment of rheumatoid arthritis (RA). Findings from 2 large trials, funded by the drugs' manufacturers, add to the existing data.

In one study, 632 patients with early RA (mean duration, 1 year) who had not undergone previous methotrexate therapy were randomized to receive 1-year courses of either weekly oral methotrexate or twice-weekly subcutaneous etanercept (10 or 25 mg). Etanercept acted more rapidly than did methotrexate: Clinical improvement was significantly greater in the 25-mg etanercept group than in the methotrexate group during the first 6 months of treatment, but differences became nonsignificant by 12 months. At 12 months, the 25-mg etanercept group had significantly less radiographically evident progression of joint erosion. Both drugs were relatively well tolerated.

In another randomized study, researchers compared weekly oral methotrexate plus intravenous infliximab (given every 4 or 8 weeks) and methotrexate plus placebo; the subjects were 428 patients with long-standing active RA (mean duration, 11 years) despite methotrexate therapy. Clinical improvement at 1 year was noted in 52 percent of combined-therapy recipients and in 17 percent of methotrexate recipients, a significant difference. There was also significantly less progression of joint damage with combined therapy. Adverse event rates were similar in the 2 groups.

Comment: The results of these 2 studies provide support for TNF-neutralizing therapy during both early and chronic phases of rheumatoid arthritis. An editorialist, although enthusiastic about TNF inhibitors, nevertheless reminds us that our understanding of their risks remains incomplete and that these agents do not cure RA.

— AS Brett

Published in Journal Watch General Medicine December 19, 2000

Citation(s):

Bathon JM et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med 2000 Nov 30 343 1586-1593.

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Lipsky PE et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. N Engl J Med 2000 Nov 30 343 1594-1602.

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Klippel JH. Biologic therapy for rheumatoid arthritis. N Engl J Med 2000 Nov 30 343 1640-1641.

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