Leflunomide for the treatment of rheumatoid arthritis: a systematic review and metaanalysis

• Published in: Journal of rheumatology Vol. 30; no. 6; pp. 1182 - 1190
• Main Authors: OSIRI, Manathip, SHEA, Beverley, ROBINSON, Vivian, SUAREZ-ALMAZOR, Maria, STRAND, Vibeke, TUGWELL, Peter, WELLS, George
• Format: Journal Article
• Language: English
• Published: Toronto, ON The Journal of Rheumatology 01-06-2003; Journal of Rheumatology Publishing
• Subjects: Arthritis, Rheumatoid - drug therapy; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Humans; Immunosuppressive Agents - therapeutic use; Isoxazoles - therapeutic use; Medical sciences; Pharmacology. Drug treatments; Randomized Controlled Trials as Topic; Human; Immunopathology; Prostaglandin-endoperoxide synthase; Isoxazole derivatives; Enzyme; Toxicity; Treatment efficiency; Diseases of the osteoarticular system; Enzyme inhibitor; Autoimmune disease; Inflammatory joint disease; Leflunomide; Metaanalysis; Non steroidal antiinflammatory agent; Chemotherapy; Chronic; Treatment; Rheumatoid arthritis; LEFLUNOMIDE RHEUMATOID ARTHRITIS SYSTEMATIC REVIEW METAANALYSIS; Oxidoreductases; Antirheumatic agent; Immunosuppressive agent; Bibliographic review
• ISSN: 0315-162X; 1499-2752

OBJECTIVE: To systematically review the evidence from clinical trials on the efficacy and toxicity of leflunomide for the
treatment of active rheumatoid arthritis (RA). METHODS: We searched Medline, Embase, Current Contents, and the Cochrane Controlled
Trial Register for human randomized controlled trials (RCT) and controlled clinical trials up to December 2001. We also hand-searched
reference lists and conference proceedings and consulted content experts. Relative benefit (RB), and weighted mean differences
or standardized mean differences with their 95% confidence interval (95% CI) were calculated. RESULTS: Six RCT totaling 2044
patients with RA were included in this review. Using specific criteria, all trials were considered of high methodological
quality. Leflunomide improved the ACR20 response rate roughly 2 times over placebo both at 6 months (RB = 1.93, 95% CI 1.51,
2.47) and at 12 months (RB = 1.99, 95% CI 1.42, 2.77). Other clinical outcomes of disease activity and function and radiological
scores were also significantly better for leflunomide patients than those taking placebo. No significant differences for most
of the outcomes were observed between leflunomide and sulfasalazine (SSZ) or methotrexate (MTX). Adverse events were more
common in the leflunomide group, but withdrawal rates were fewer than for placebo. Overall, withdrawal rates and adverse events
in the leflunomide group were not different from SSZ or MTX. CONCLUSION: Leflunomide improves all clinical outcomes and delays
radiographic progression at 6 and 12 months of RA treatment compared to placebo. Its efficacy and adverse events at 2 years
of treatment are comparable to SSZ and MTX. Longterm efficacy and toxicity remain to be established.