Efficacy of leflunomide 100mg weekly compared to low dose methotrexate in patients with active rheumatoid arthritis. Double blind, randomized clinical trial

Reumatol Clin. Sep-Oct 2012;8(5):243-9. doi: 10.1016/j.reuma.2012.03.013. Epub 2012 Jul 2.


Objective: To determine the clinical efficacy and safety of Leflunomide (LFN) 100 mg/week compared to low dose Methotrexate (MTX) 10 mg/week in a double-blind, randomized, controlled trial with 52 weeks of follow up in Rheumatoid Arthritis (RA) patients.

Patients and methods: Patients who met ARC1987 criteria for RA were included. All patients had medical records, including laboratory tests and hand X-rays. Clinical evaluations for improvement and ACR and EULAR response criteria were performed. Statistical analysis for independent's samples between both groups defined a P value of ≤.05. Safety was evaluated by comparing the proportion of adverse events (AE) registered.

Results: Of 90 patients screened; five were withdrawn; the remaining 85 patients were randomised: 43 LFN and 42 MTX. Sixty-three patients completed the study; 72% in the LFN group and 74.4% in the MTX group. ACR20 improvement criteria were achieved by LFN group in 90.3%, and in MTX 78.1% (P=.14) at week 52. EULAR improvement criteria applied at the end point showed a DAS28 score for the LFN group of 3.45, and for the MTX group was 3.67(P=.43). Total withdrawals, including loss during follow up, AE and lack of efficacy for each group was 12 patients in the LFN group, and 10 patients in the MTX group. Regarding safety, no serious AE of a life threatening nature were reported.

Conclusions: These outcomes confirm that LFN 100 mg/week offers an adequate and sustained improvement effect on the clinical manifestations of RA, similar to low dose treatment with MTX 10 mg/every week after 52 weeks of follow up; it may be a good therapeutic option alone or in combination with others anti-rheumatic drugs.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Chemical and Drug Induced Liver Injury / etiology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Eruptions / etiology
  • Female
  • Humans
  • Immunocompromised Host
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use
  • Infections / etiology
  • Isoxazoles / administration & dosage
  • Isoxazoles / adverse effects
  • Isoxazoles / therapeutic use*
  • Leflunomide
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Severity of Illness Index
  • Treatment Outcome


  • Antirheumatic Agents
  • Immunosuppressive Agents
  • Isoxazoles
  • Leflunomide
  • Methotrexate