Treatment of active rheumatoid arthritis with leflunomide: two year followup of a double blind, placebo controlled trial versus sulfasalazine

Objective-Recent studies have demonstrated the short term efficacy of leflu nomide. This study evaluates the efficacy and safety of leflunomide and sul fasalazine in rheumatoid arthritis over a two year follow up period. Methods-358 patients with rheumatoid arthritis in a double blind trial were randomly allocated to receive either leflunomide 20 mg/day, placebo, or su lfasalazine 2 g/day. Those completing six months of treatment (n=230) were given the option to continue in 12 (n=168) and 24 (n=146) month double blin ded extensions; the placebo group switched to sulfasalazine. This report co mpares efficacy and safety of leflunomide with sulfasalazine in the 6, 12, and 24 month patient cohorts. Results-The efficacy seen at six months was maintained at 12 and 24 months. Twenty four month cohorts on leflunomide showed significant improvement co mpared with sulfasalazine in doctor (-1.46 upsilon -1.11, p=0.03) and patie nt (-1.61 upsilon -1.04, p <0.001) global assessments, ACR20% response (82% upsilon 60%, p <0.01), and functional ability (Delta mean HAQ -0.65 upsilo n -0.36, p=0.0149; Delta HAQ disability index -0.89 upsilon -0.60, p=0.059) . Improvement in other variables was comparable for the two drugs, includin g slowing of disease progression. Improved HAQ scores in 6, 12, and 24 mont h leflunomide cohorts were seen in both non-responders (24%, 29%, 35%, resp ectively upsilon sulfasalazine 8%, 10%, 27%) and ACR20% responders (lefluno mide 63%, 62%, 66% upsilon sulfasalazine 50%, 64%, 44%). Leflunomide is wel l tolerated at doses of 20 mg. No unexpected adverse events or late toxicit y were noted during the two year period. Diarrhoea, nausea, and alopecia we re less frequent with continued treatment. Conclusion-These long term data confirm that leflunomide is an efficacious and safe disease modifying antirheumatic drug.