Leflunomide or methotrexate for juvenile rheumatoid arthritis

N Engl J Med. 2005 Apr 21;352(16):1655-66. doi: 10.1056/NEJMoa041810.


Background: We compared the safety and efficacy of leflunomide with that of methotrexate in the treatment of polyarticular juvenile rheumatoid arthritis in a multinational, randomized, controlled trial.

Methods: Patients 3 to 17 years of age received leflunomide or methotrexate for 16 weeks in a double-dummy, blinded fashion, followed by a 32-week blinded extension. The rates of American College of Rheumatology Pediatric 30 percent responses (ACR Pedi 30) and the Percent Improvement Index were assessed at baseline and every 4 weeks for 16 weeks and every 8 weeks during the 32-week extension study.

Results: Of 94 patients randomized, 86 completed 16 weeks of treatment, 70 of whom entered the extension study. At week 16, more patients in the methotrexate group than in the leflunomide group had an ACR Pedi 30 response (89 percent vs. 68 percent, P=0.02), whereas the values for the Percent Improvement Index did not differ significantly (-52.87 percent vs. -44.41 percent, P=0.18). In both groups, the improvements achieved at week 16 were maintained at week 48. The most common adverse events in both groups included gastrointestinal symptoms, headache, and nasopharyngeal symptoms. Aminotransferase elevations were more frequent with methotrexate than with leflunomide during the initial study and the extension study.

Conclusions: In patients with polyarticular juvenile rheumatoid arthritis, methotrexate and leflunomide both resulted in high rates of clinical improvement, but the rate was slightly greater for methotrexate. At the doses used in this study, methotrexate was more effective than leflunomide.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Alanine Transaminase / blood
  • Analysis of Variance
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / pharmacokinetics
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Juvenile / drug therapy*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Isoxazoles / adverse effects
  • Isoxazoles / pharmacokinetics
  • Isoxazoles / therapeutic use*
  • Leflunomide
  • Logistic Models
  • Male
  • Methotrexate / adverse effects
  • Methotrexate / pharmacokinetics
  • Methotrexate / therapeutic use*
  • Severity of Illness Index


  • Antirheumatic Agents
  • Isoxazoles
  • Alanine Transaminase
  • Leflunomide
  • Methotrexate