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Article

Safety and effectiveness of leflunomide in the treatment of patients with active rheumatoid arthritis

  1. Vlastimir Mladenovic MD1,
  2. Zlatko Domljan MD, PhD2,
  3. Blaz Rozman MD, PhD2,
  4. Ivo Jajic MD3,
  5. Dimitrije Mihajlovic MD4,
  6. Jovan Dordevic PhD4,
  7. Milan Popovic MD5,
  8. Miroslava Dimitrijevic MD6,
  9. Milutin Zivkovic MD7,
  10. Giles Campion MD8,
  11. Predrag Musikic MD9,
  12. Iris Löw-Friedrich MD, CH.Oed, Dipl. Stat10,*,
  13. Christine Oed MD10,
  14. Hildegard Seifert MD10,
  15. Vibeke Strand MD11

Article first published online: 9 DEC 2005

DOI: 10.1002/art.1780381111

Issue

Arthritis & Rheumatism

Arthritis & Rheumatism

Volume 38, Issue 11, pages 1595–1603, November 1995

Additional Information

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

Author Information

  1. 1

    Institute of Rheumatology, Beograd, Yugoslavia

  2. 2

    University Medical Center, Ljubljana, Slovenia

  3. 3

    University Clinical Hospital, Zagreb, Croatia

  4. 4

    Institute for Rheumatic and Cardiovascular Disease, Niska Banja, Yugoslavia

  5. 5

    Clinic at Military Medical Academy, Belgrade, Yugoslavia

  6. 6

    University School of Pharmacy, Belgrade, Yugoslavia

  7. 7

    Institut Igale, Hersag Nevi, Yugoslavia

  8. 8

    Hoechst AG, Wiesbaden Germany (currently with SmithKline Beecham, King of Prussia, Pennsylvania)

  9. 9

    Hoechst AG (currently with Synergen BV, The Hague, Netherlands)

  10. 10

    Hoechst AG

  11. 11

    Consultant to Hoechst AG, and Stanford University, Stanford, California

*Hoechst AG, Clinical Research, D65174 Wiesbaden, Germany

Publication History

  1. Issue published online: 9 DEC 2005
  2. Article first published online: 9 DEC 2005
  3. Manuscript Revised: 6 JUN 1995
  4. Manuscript Accepted: 23 MAR 1995

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Abstract

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.

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