The efficacy and safety of leflunomide in patients with active rheumatoid arthritis: a five-year followup study

Arthritis Rheum. 2003 Jun;48(6):1513-20. doi: 10.1002/art.11015.


Objective: To investigate the efficacy and safety of leflunomide beyond 2 years in a multinational, open-label extension of 2 phase III double-blind studies.

Methods: Patients with rheumatoid arthritis (RA) who received leflunomide (100 mg/day for 3 days, 10 mg/day or 20 mg/day thereafter) in the 2 phase III studies and who completed 2 years of treatment were offered inclusion in the open-label extension phase and were maintained on the same dosage of leflunomide. The American College of Rheumatology revised criteria for 20% improvement (ACR20), ACR50, and ACR70 response rates, the Stanford Health Assessment Questionnaire (HAQ) scores, and C-reactive protein (CRP) levels were assessed. Safety measures included monitoring of adverse events and laboratory values.

Results: A total of 214 patients (mean age 57 years) were treated with leflunomide for >2 years; 74.8% of the patients were female. The mean disease duration was 4.1 years (range 0.1-26.6 years), and in 44% of patients, RA was first diagnosed within 2 years of entry into the phase III studies. The mean duration of leflunomide treatment was 4.6 years (range 2.8-5.8 years), and 32% of patients had received no previous treatment with disease-modifying antirheumatic drugs. ACR20, ACR50, and ACR70 response rates and HAQ scores at 1 year were maintained through year 4 or until the end point. No new types of adverse events were observed, and liver function was normal at baseline and at the end point in the majority of patients.

Conclusion: The improvements in both functional ability and physician-based efficacy measures seen with leflunomide after 1 year were maintained for up to 5 years (maximum treatment duration 5.8 years), demonstrating that the early efficacy of leflunomide in patients with RA is sustained long-term, and that the long-term safety profile of leflunomide is no different from that observed in phase III trials.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / physiopathology
  • C-Reactive Protein / analysis
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Health Status
  • Humans
  • International Cooperation
  • Isoxazoles / therapeutic use*
  • Leflunomide
  • Male
  • Severity of Illness Index
  • Surveys and Questionnaires
  • Treatment Outcome


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antirheumatic Agents
  • Isoxazoles
  • C-Reactive Protein
  • Leflunomide