Safety and effectiveness of leflunomide in the treatment of patients with active rheumatoid arthritis
Article first published online: 9 DEC 2005
Copyright © 1995 American College of Rheumatology
Arthritis & Rheumatism
Volume 38, Issue 11, pages 1595–1603, November 1995
How to Cite
Mladenovic, V., Domljan, Z., Rozman, B., Jajic, I., Mihajlovic, D., Dordevic, J., Popovic, M., Dimitrijevic, M., Zivkovic, M., Campion, G., Musikic, P., Löw-Friedrich, I., Oed, C., Seifert, H. and Strand, V. (1995), Safety and effectiveness of leflunomide in the treatment of patients with active rheumatoid arthritis. Arthritis & Rheumatism, 38: 1595–1603. doi: 10.1002/art.1780381111
- Issue published online: 9 DEC 2005
- Article first published online: 9 DEC 2005
- Manuscript Revised: 6 JUN 1995
- Manuscript Accepted: 23 MAR 1995
Objective. To assess the safety and effectiveness of leflunomide versus placebo in patients with active rheumatoid arthritis (RA) treated for 6 months.
Methods. Four hundred two patients were randomly assigned to receive placebo or leflunomide at 5 mg, 10 mg, or 25 mg daily. A washout period of 6–12 weeks from prior second-line therapy was required.
Results. Statistically significant improvement in primary and secondary outcome measures, as well as by responder analyses, occurred in the 10-mg and 25-mg dosage groups compared to placebo. Twenty-one patients (7.0%) in the active treatment groups withdrew due to adverse events (AEs). The incidence of AEs was higher with leflunomide than with placebo. Gastrointestinal symptoms, weight loss, allergic reactions, skin rash, and reversible alopecia were more common in the 10-mg and 25-mg dosage groups. The incidence of infections was similar between the treatment and placebo groupsno opportunistic infections were seen. Transient elevations in liver function studies were noted in a small number of patients.
Conclusion. Leflunomide is effective in daily doses of 10 mg and 25-mg in patients with active RA. Improved efficacy at the 25-mg dose was associated with a higher incidence of AEs. Randomized, placebocontrolled trials using daily doses of 10 mg and 20 mg are under way in the US and Europe to confirm these positive results.