In a recently published study (Lancet 353:259-266, 1999), Smolen et al reported on the results of a Phase III trial of leflunomide (AravaTM) for the treatment of rheumatoid arthritis (RA). 358 patients were randomly assigned to one of three treatments for 6 months: leflunomide (100 mg daily on days 1-3, then 20 mg daily); sulfasalazine (0.5g qd, titrated up to 2.0g qd); or placebo. The numbers of patients who responded to treatment, as assessed by the American College of Rheumatology 20% criteria, were significantly higher for the two treatment groups compared to the placebo group: leflunomide 55%, sulfasalazine 56%, placebo 29% (p=0.0001, leflunomide vs. placebo, sulfasalazine vs. placebo). Furthermore, radiologic bone progression, as measured by the Larsen score, was significantly reduced in the leflunomide and sulfasalazine groups compared to placebo. The most common adverse events reported by patients treated with leflunomide were diarrhea, nausea, rash, and alopecia. Two of the 133 patients treated with leflunomide were withdrawn from the study due to elevated liver function tests.
Editorial comment: These data confirm Phase II studies showing that leflunomide is efficacious in reducing the joint pain and swelling of RA. More importantly, they demonstrate that leflunomide is a disease modifying agent (i.e., it slows radiologic bone progression. Sulfasalazine also performed surprisingly well in this study (comparable to leflunomide). The ability to detect significant radiologic progression in just 6 months was another surprise. For more information about leflunomide and sulfasalazine.