Treatment of DMARD-Resistant Active Rheumatoid Arthritis Patients with Leflunomide: Central Taiwan Experience

Abstract

Objective: To examine the efficacy and safety of leflunomide (LEF) for patients with active rheumatoid arthritis (RA) who have been resistant to conventional disease-modifying antirheumatic drugs (DMARDs) including methotrexate (MTX). Methods: In this open-label, 48-week study, 61 patients with RA who remained active (DAS28≧5.1) despite therapy with conventional DMARDs for at least 4 months were given LEF, 10mg/day. Patients were required to have been receiving a stable dosage of MTX 12.5mg/week for at least 8 weeks prior to study enrollment. Efficacy variables were morning stiffness, patient global assessment, physician assessment, number of swollen joints, number of tender joints, IgM rheumatoid factor (RF), IgA RF, Wintrobe erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and platelet count. Safety measures included monitoring of adverse events and laboratory values. Results: Sixty active RA patients completed one year of treatment. The mean DAS28 of patients before LEF were 6.3±0.9. Measurements after 4, 12, 24, and 48 weeks of LEF treatment all differed significantly from baseline, including tender joint count, swollen joint count, patient global assessment, physician global assessment, DAS28, and serology index of ESR, CRP, and RF. Changes between weeks 4 and 12, week 4 and 24, weeks 4 and 48 were also significant in variables described. The changes among week 12, 24 and 48 were of no significance. LEF efficacy showed a plateau of response after 12 months with treatment of LEF. However, improvement was sustained to the end point of the study. In these 61 patients, LEF treatment was generally well tolerated with the exception of elevation of liver enzyme. Most patients with abnormal liver function returned to normal range without discontinuation of LEF. Only one patient withdrew from the study for persistent elevation of liver enzymes. The most commonly mentioned adverse events of diarrhea, nausea, stomatitis, upper respiratory tract infection, and rash were found and most adverse events were rated as mild in severity. No additional side effect was observed in combination therapy of MTX with LEF. Conclusion: LEF has therapeutic potential in DMARD-resistant active RA patients. It is a logical alternative for patients who have an incomplete response to optimal effective DMARDs. Results indicate that combination therapy with LEF is a safe and effective treatment for DMARD-resistant RA, with clinical benefit sustained over one year of treatment without evidence of new or increased toxicity.