Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial

Background Phase II trials of leflunomide, an inhibitor of de-novo pyrimidi ne synthesis, have shown efficacy in rheumatoid arthritis. This double-blin d randomised trial compared leflunomide with placebo and sulphasalazine in active rheumatoid arthritis. Methods 358 patients were randomly assigned leflunomide (100 mg daily on da ys 1-3, then 20 mg daily), placebo, or sulphasalazine (0.5 g daily, titrate d progressively to 2.0 g daily at week 4.). The primary endpoints were tend er and swollen joint counts and investigator's and patient's overall assess ments. Analyses were by intention to treat. Findings The mean changes in the leflunomide, placebo, and sulphasalazine g roups were -9.7, -4.3, and -8.1 for tender joint count; -7.2, -3.4, and -6. 2 for swollen joint count; -1.1, -0.3, and -1.0 for physician's overall ass essment; and -1.1, -0.4, and -1.1 for patient's overall assessment. Lefluno mide and sulphasalazine were significantly superior to placebo (p = 0.0001 for joint counts; p < 0.001 for assessments). Radiographic disease progress ion was significantly slower with leflunomide and sulphasalazine than with placebo (p < 0.01). Most common adverse events with leflunomide were diarrh oea (17%), nausea (10%), alopecia (8%), and rash (10%). Transiently abnorma l liver function was seen in three leflunomide-group patients and five sulp hasalazine-group patients. There were two cases of reversible agranulocytos is in the sulphasalazine group. Interpretation Leflunomide was more effective than placebo in treatment of rheumatoid arthritis and showed similar efficacy to sulphasalazine. Lefluno mide was well tolerated, This drug may be a useful option as a disease-modi fying antirheumatic drug.