Leflunomide in monotherapy of rheumatoid arthritis: meta-analysis of randomized trials.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic systemic disease of the connective tissue that leads to progressive joint destruction, disability, withdrawal from occupational activity, and premature death.

OBJECTIVES: The aim of the paper was to evaluate the efficacy and safety of leflunomide compared with placebo, methotrexate, and sulfasalazine in monotherapy of RA.

PATIENTS AND METHODS: A systematic search of databases (MEDLINE, EMBASE, Cochrane CENTRAL) was performed. Only randomized blind trials were included into the analysis. The quality of the trials was assessed by the Jadad scale. A quantitative synthesis of the results was performed (meta-analysis).

RESULTS: The analysis included 7 trials involving 2861 patients (1432 on leflunomide, 312 on placebo, 922 on methotrexate, and 133 on sulfasalazine). Leflunomide, compared with placebo, increased the probability of the American College of Rheumatology 20% improvement (ACR20) response 2-fold (relative risk [RR], 2.02; 95% CI, 1.46-2.80) and the probability of ACR50 response 4-fold (RR, 4.36; 95% CI, 2.33-8.17), after 1 year of treatment. Efficacy of leflunomide did not differ from that of methotrexate with reference to the majority of endpoints. Leflunomide showed partial superiority over methotrexate in the percentage of patients obtaining ACR50 and ACR70 response, doctor's assessment of the disease activity, reduction in C-reactive protein (CRP) levels, and improvement of the quality of life (assessed with the modified health assessment questionnaire [HAQ]). Sulfasalazine showed partial superiority in the reduction of erythrocyte sedimentation rate, while leflunomide was superior to sulfasalazine the ACR20 and ACR50 clinical response, quality of life (assessed with the HAQ), doctor's and patient's assessment of the disease activity, and reduction in CRP levels.

CONCLUSIONS: There were no significant differences between the effects of treatment with leflunomide and methotrexate or sulfasalazine, but leflunomide monotherapy proved more effective than placebo in relieving symptoms and signs of RA.