Skip to main content
SpringerLink
Log in

Leflunomide

  • New Drug Profile
  • Published:
Clinical Immunotherapeutics Aims and scope Submit manuscript

Summary

  • ▲ Leflunomide is a novel isoxazole derivative with immunosuppressant and anti-inflammatory properties. It has been most extensively evaluated in patients with rheumatoid arthritis and may be categorised as a disease-modifying antirheumatic drug (DMARD).

  • ▲ The drug appears to have a unique mechanism of action involving inhibition of de novo pyrimidine synthesis in immune cells.

  • ▲ In animal models of arthritis, leflunomide demonstrated a number of beneficial effects including reduced inflammation and joint stiffness.

  • ▲ In patients with rheumatoid arthritis, leflunomide 10 or 25 mg/day for 24 weeks significantly improved various outcome measures such as patient global assessment and swollen joint scores compared with placebo. Efficacy seems to be similar to that of established DMARDs.

  • ▲ Relative to established DMARDs, leflunomide appears to have a rapid onset of action. The most frequently reported adverse events with leflunomide are gastrointestinal.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bartlett RR, Anagnostopulos H, Zielinski T, et al. Effects of leflunomide on immune responses and models of inflammation. Springer Semin Immunopathol 1993 Apr; 14: 381–94

    Article  PubMed  CAS  Google Scholar 

  2. Cao WW, Kao PN, Chao AC, et al. Mechanism of the antiproliferative action of leflunomide: A77 1726, the active metabolite of leflunomide, does not block T-cell receptor-mediated signal transduction but its antiproliferative effects are antagonized by pyrimidine nucleosides. J Heart Lung Transplant 1995 Nov–Dec; 14 (Pt 1): 1016–30

    PubMed  CAS  Google Scholar 

  3. Cherwinski HM, Cohn RG, Cheung P, et al. The immunosuppressant leflunomide inhibits lymphocyte proliferation by inhibiting pyrimidine biosynthesis. J Pharmacol Exp Ther 1995 Nov; 275: 1043–9

    PubMed  CAS  Google Scholar 

  4. Cherwinski HM, Byars N, Ballaron SJ, et al. Leflunomide interferes with pyrimidine mucleotide biosynthesis. Inflamm Res 1995 Aug; 44: 317–22

    Article  PubMed  CAS  Google Scholar 

  5. Morris RE. Mechanisms of action of new immunosuppressive drugs. Kidney Int 1996; 49 Suppl. 53: S26–38

    Google Scholar 

  6. Zielinski T, Zeitter D, Mullner S, et al. Leflunomide, a reversible inhibitor of pyrimidine biosynthesis? Inflamm Res 1995; 44 Suppl. 2: S207–8

    Article  PubMed  CAS  Google Scholar 

  7. Greene S, Watanabe K, Braatztrulson J, et al. Inhibition of dihydroorotate dehydrogenase by the immunosuppressive agent leflunomide. Biochem Pharmacol 1995 Sep 7; 50: 861–7

    Article  PubMed  CAS  Google Scholar 

  8. Atluru S, Atluru D. Evidence that genistein, a protein-tyroxine kinase inhibitor, inhibits CD28 monoclonal-antibody-stimulated human T cell proliferation. Transplantation 1991; 51(2): 448–50

    Article  PubMed  CAS  Google Scholar 

  9. Cao W, Chao AC, Morris RE. Leflunomide, a new immunosuppressant, inhibits tyrosine kinase, calcium signaling and DNA synthesis in vascular smooth muscle [abstract]. FASEB J 1994 Mar 15; 8 (Pt 1): 486

    Google Scholar 

  10. Mattar T, Kochhar K, Bartlett R, et al. Inhibition of the epidermal growth factor receptor tyrosine kinase activity by leflunomide. FEBS Lett 1993 Nov 15; 334: 161–4

    Article  PubMed  CAS  Google Scholar 

  11. Bartlett RR, Schleyerbach R. Immunopharmacological profile of a novel isoxazol derivative, HWA 486, with potential antirheumatic activity. I. Disease modifying action on adjuvant arthritis of the rat. Int J Immunopharmacol 1985; 7: 7–18

    Article  PubMed  CAS  Google Scholar 

  12. Pasternak RD, Wadopian NS, Wright RN, et al. Disease modifying activity of HWA 486 in rat adjuvant-induced arthritis. Agents Actions 1987 Aug; 21: 241–3

    Article  PubMed  CAS  Google Scholar 

  13. Giant TT, Mikecz K, Bartlett RR, et al. Immunomodulation of proteoglycan-induced progressive polyarthritis by leflunomide. Immunopharmacology 1992 Mar–Apr; 23: 105–16

    Article  Google Scholar 

  14. Giant TT, Mikecz K, Brennan F, et al. Suppression of autoimmune responses and inflammatory events by leflunomide in an animal model for rheumatoid arthritis. Agents Actions 1994 Aug; 41 (Spec. issue): C267–70

    Article  Google Scholar 

  15. Dimitrijevic M, Kosec D, Popeskovic L, et al. Influence of leflunomide (HWA 486) on immune system activation in RA [abstract]. Rev Esp Reumatol 1993 Jul; 20 Suppl. 1: 398

    Google Scholar 

  16. Dimitrijevic M, Stupar N, Pilipovic N. Leflunomide in the treatment of patients with severe rheumatoid arthritis: influence on immunological parameters [abstract]. Clin Exp Rheumatol 1995 Sep–Oct; 13 Suppl. 12: 56

    Google Scholar 

  17. Richardson C, Emery P. New therapies for rheumatoid arthritis. Br J Clin Pract 1995; 49(3): 135–9

    PubMed  CAS  Google Scholar 

  18. Furst DE. Cyclosporin, leflunomide and nitrogen mustard. Baillieres Clin Rheumatol 1995 Nov; 9: 711–29

    Article  PubMed  CAS  Google Scholar 

  19. Mladenovic V, Domljan Z, Rozman B, et al. Safety and effectiveness of leflunomide in the treatment of patients with active rheumatoid arthritis: results of a randomized, placebo-controlled, phase II study. Arthritis Rheum 1995 Nov; 38: 1595–603

    Article  PubMed  CAS  Google Scholar 

  20. Carlson RP. Newer immunosuppressive drugs and other agents for the treatment of rheumatoid arthritis — an update. Expert Opin Invest Drug 1995 Sep; 4: 853–9

    Article  CAS  Google Scholar 

  21. Lucien J, Dias VC, LeGatt DF. Blood distribution and single-dose pharmacokinetics of leflunomide. Ther Drug Monit 1995 Oct; 17: 454–9

    Article  PubMed  CAS  Google Scholar 

  22. Roethig H-J, Collins J, Harnisch L, et al. The effect of activated charcoal and cholestyramine on the pharmacokinetics of leflunomide [abstract no. PIII-65]. Clin Pharmacol Ther 1996; 59(2): 204

    Article  Google Scholar 

  23. Campion G, Löw-Friedrich I, Oed C, et al. Comparison of different dosing regimens of leflunomide in the treatment of active rheumatoid arthritis [abstract]. Scand J Rheumatol 1994 Suppl. 98: abstr. 140

    Google Scholar 

  24. Domljan Z, Popovic M, Mladenovic V, et al. Efficacy and safety of leflunomide in the treatment of patients with rheumatoid arthritis (RA) [abstract]. Arthritis Rheum 1993 Sep; 36 Suppl.: 56

    Google Scholar 

  25. Dias VC, Lucien J, LeGatt DF, et al. Measurement of the active leflunomide metabolite (A77 1726) by reverse-phase high-performance liquid chromatography. Ther Drug Monit 1995 Feb; 17: 84–8

    Article  PubMed  CAS  Google Scholar 

  26. Dekleva-Djordjevic J, Radunovic L, Musikic P, et al. Adverse effects of leflunomide treatment in patients with rheumatoid arthritis at the Zemun clinical centre [abstract]. Clin Exp Rheumatol 1995 Sep–Oct; 13 Suppl. 12: 57

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand

    Greg L. Plosker & Antona J. Wagstaff

Authors
  1. Greg L. Plosker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antona J. Wagstaff
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Plosker, G.L., Wagstaff, A.J. Leflunomide. Clin. Immunother. 6, 300–305 (1996). https://doi.org/10.1007/BF03259090

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03259090

Keywords

Search

Navigation