Leflunomide for treating rheumatoid arthritis

Cochrane Database Syst Rev. 2003;2002(1):CD002047. doi: 10.1002/14651858.CD002047.


Background: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease. Leflunomide, as an inhibitor of pyrimidine synthesis, has a different mechanism of action than other existing disease modifying anti-rheumatic drugs (DMARD).

Objectives: To determine the efficacy and toxicity of leflunomide compared to placebo or other DMARDs in the treatment of RA.

Search strategy: We conducted a search in MEDLINE, EMBASE, Current Contents and the Cochrane Controlled Trial Register for trials up to December 2001. We also hand-searched reference lists and consulted content experts.

Selection criteria: Two independent reviewers selected the trials that met predetermined inclusion criteria.

Data collection and analysis: Two independent reviewers extracted data and assessed methodologic quality using standardized forms.

Main results: Six trials were included in this review. Using the ACR20 improvement criteria, there was an absolute difference in improvement of 28% (95% confidence interval: 21 - 35%) favouring leflunomide (232 out of 413 leflunomide treated patients compared to 89 out of 311 placebo patients met the criteria). There was no difference in ACR20 response rate between the patients treated with leflunomide and SSZ or MTX at 6 and 12 months. Other clinical outcomes were improved significantly in the leflunomide group compared to placebo but not different from SSZ or MTX. Withdrawals due to adverse events with leflunomide were 10% greater than placebo (70 out of 416 compared to 18 out of 311 respectively). Important adverse events included gastrointestinal symptoms, elevated liver function tests, alopecia, and infections. Overall adverse events and withdrawals in the leflunomide group were not significantly different from SSZ or MTX.

Reviewer's conclusions: Leflunomide appears to improve all clinical outcomes and delay radiologic progression at both 6 and 12 months of treatment compared to placebo. Its efficacy and adverse events at 2 years of treatment are comparable to SSZ and MTX. Long-term efficacy and toxicity remains to be established.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Humans
  • Isoxazoles / therapeutic use*
  • Leflunomide
  • Methotrexate / therapeutic use
  • Randomized Controlled Trials as Topic
  • Sulfasalazine / therapeutic use


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antirheumatic Agents
  • Isoxazoles
  • Sulfasalazine
  • Leflunomide
  • Methotrexate