Clinical experience with leflunomide in rheumatoid arthritis. Leflunomide Investigators' Group.

Leflunomide is a novel isoxazol drug with disease modifying properties for the treatment of rheumatoid arthritis (RA). Several Phase II trials have been completed and 3 large Phase III trials are nearing completion. A multicenter Phase II randomized, double blind, placebo controlled, 24 week study of 402 patients with active RA revealed that leflunomide 25 mg once daily was significantly (p < 0.05) superior to placebo in all primary and secondary outcome measures; leflunomide 10 mg daily was also statistically superior to placebo for all outcome measures except tender joint count and score. Significantly (p < 0.05) more patients responded to leflunomide 10 and 25 mg than to placebo. Leflunomide appears to be well tolerated in patients treated for up to 18 months. Gastrointestinal events, weight loss, rash/allergic reactions, and reversible alopecia were the most frequently reported drug related adverse events. Patients treated with leflunomide were not more susceptible to infections than those given placebo. Based upon the results of a population based pharmacokinetic/pharmacodynamic model, leflunomide 20 mg was selected as optimal dose for the Phase III studies; these are 6 to 12 month multicenter, randomized, double blind, controlled trials that include as active comparators methotrexate and sulfasalazine. Once-daily administration of leflunomide is effective in patients with active RA.