Objective: To determine the efficacy and safety of the combination of leflunomide and methotrexate for the treatment of patients with active rheumatoid arthritis (RA) in an open, non-comparative, multicentre trial.
Methods: Seventy-four patients with active RA were enrolled to receive concomitantly leflunomide (no loading dose, 10 mg/day) and methotrexate (starting at 7.5 mg/week and titrating up to 15 mg/week) for 20 weeks. The primary end-point was a 20% improvement in the American College of Rheumatology (ACR) criteria at 20 weeks. Safety measures included evaluation of adverse events at each visit and laboratory data, including haematology and liver function tests. Intention-to-treat analyses were conducted.
Results: Sixty-five patients completed 20 weeks of treatment, and 71.6% were responders based on the ACR20 criteria. After 20 weeks, the mean changes were -16.3 for tender joint count, -12.0 for swollen joint count, -44.0 for physician global assessment, -34.3 for patient global assessment, -22.7 for erythrocyte sedimentation rate, and -0.65 for the Health Assessment Questionnaire score. Adverse events occurred in 40.5% of the patients, and were considered serious in four patients who discontinued therapy. Abnormal liver function was noted for 16 patients (21.6%). Two of these patients were withdrawn from the study; after discontinuing the medication, their liver function recovered fully.
Conclusion: THE combination of leflunomide and methotrexate was effective and well tolerated in the treatment of active RA patients. This combination may be a useful option as an initial treatment for active RA before starting biological agents.