title: Leflunomide for the treatment of rheumatoid arthritis: a systematic review and metaanalysis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Faculty of Medicine, Chulalongkorn University Hospital, Bangkok, Thailand.
authors.forename: Manathip
authors.initials: M
authors.lastname: Osiri
authors.forename: Beverley
authors.initials: B
authors.lastname: Shea
authors.forename: Vivian
authors.initials: V
authors.lastname: Robinson
authors.forename: Maria
authors.initials: M
authors.lastname: Suarez-Almazor
authors.forename: Vibeke
authors.initials: V
authors.lastname: Strand
authors.forename: Peter
authors.initials: P
authors.lastname: Tugwell
authors.forename: George
authors.initials: G
authors.lastname: Wells
mesh_terms: D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007555:Isoxazoles / Q000627:therapeutic use*; D000077339:Leflunomide; D016032:Randomized Controlled Trials as Topic
chemical_list: D007166:Immunosuppressive Agents; D007555:Isoxazoles; D000077339:Leflunomide