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Leflunomide therapy for autoimmune diseases

  • Angela Gause
  • Claudia Metzler
  • Eva Reinhold-Keller
  • Wolfgang L. Gross

Abstract

Leflunomide has been shown to be an effective drug for the treatment of inflammatory arthritis in animal models and in humans. By its action on the enzyme dehydro-orotat-dehydrogenase it interferes with pyrimidine nucleoside biosynthesis and acts on the proliferation of activated lymphocytes (Fox et al. 1999, Case 2001). Because of its immunomodulatory actions it is a drug which will be interesting also for other autoimmune diseases; further mechanisms beside the lymphocyte inhibitory effect may contribute to its effectiveness. The scope of this article is not a complete review of mechanisms and applications of leflunomide but a summary of new insights in action and applications in autoimmune diseases other than rheumatoid arthritis for further potential use.

Keywords

Herpes Simplex Virus Type Giant Cell Arteritis Bullous Pemphigoid Antineutrophil Cytoplasmic Antibody Pyrimidine Nucleoside 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Case JP (2001) Old and new drugs used in rheumatoid arthritis: a historical perspective. Part 2: the newer drugs and drug strategies. Am J Ther 8: 163–179PubMedCrossRefGoogle Scholar
  2. Choi HK, Liu S, Merkel PA, Colditz GA, Niles JL (2001) Diagnostic performance of antineutrophil cytoplasmic antibody tests for idiopathic vasculitides: metaanalysis with a focus on antimyeloperoxidase antibodies. J Rheumatol 28: 1584–1590PubMedGoogle Scholar
  3. de Groot K, Reinhold-Keller E, Tatsis E, Paulsen J, Heller M, Nolle B, Gross WL (1996) Therapy for the maintenance of remission in sixty-five patients with generalized Wegener’s granulomatosis: methotrexate versus trimethoprim/sulfamethoxazole. Arthritis Rheum 39: 2052–2061PubMedCrossRefGoogle Scholar
  4. Fox RI, Herrmann ML, Frangou CG, Wahl GM, Morris RE, Kirschbaum BJ (1999) How does leflunomide modulate the immune response in rheumatoid arthritis BioDrugs 12: 301–315PubMedCrossRefGoogle Scholar
  5. Gause AL, Lamprecht P, Voswinkel J, Lilienthal T, Gross WL (2001) Effectiveness of TNF-alpha blockade with infliximab in refractory Wgener’s granulomatosis. Clin Immunol 99: 176 Gross WL, Trabandt A, Reinhold-Keller E (2000) Diagnosis and evaluation of vasculitis. Rheumatology 39: 245–252Google Scholar
  6. Hagen EC, Daha MR, Hermans J, Andrassy K, Csernok E, Gaskin G, Lesavre P, Liidemann J, Rasmussen N, Sinico RA, Wiik A, van der Woude FJ (1998) Diagnostic value of standardized assays for anti-neutrophil cytoplasmic antibodies in idiopathic systemic vasculitis: EC/BCR project for ANCA assay standardization (1998). Kidney Int 53: 743–753PubMedCrossRefGoogle Scholar
  7. Knight DA, Hejmanowski AQ, Dierksheide JE, Williams JW, Chong AS, Waldman WJ (2001) Inhibition of herpes simplex virus type 1 by the experimental immunosuppressive agent leflunomide. Transplantation 71: 170–174PubMedCrossRefGoogle Scholar
  8. Kraan MC, Reece RJ, Barg EC, Smeets TJM, Farnell J, Rosenburg R, Veale DJ, Breedveld FC, Emery P, Tak PP (2000) Modulation of inflammation and metalloproteinase expression in synovial tissue by leflunomide and methotrexate in patients with active rheumatoid arthritis: findings in a prospective, randomized, double-blind, parallel-design clinical trial in thirty-nine patients at two centers. Arthritis Rheum 43: 1820–1830PubMedCrossRefGoogle Scholar
  9. Langford CA, Sneller MC (2001) Update on the diagnosis and treatment of Wegener’s granulomatosis. Adv Intern Med 46: 177–206PubMedGoogle Scholar
  10. Manna SK, Mukhopadhyay A, Aggarwal BB (2000) Leflunomide suppresses TNF-induced cellular responses: effects on NF-kappa B, activator protein-1,c-Jun N-terminal protein kinase, and apoptosis. J Immunol 165: 5962–5969PubMedGoogle Scholar
  11. Metzler C, Loew-Friedrich J, Reinhold-Keller E, Fink C, Lamprecht P, Gross WL (1999) Maintenance of remission with leflunomide in Wegener’s granulomatosis. Arthritis Rheum 42 Suppl: 1466 Nousari HC, Anhalt GJ (2000) Bullous pemphigoid treated with leflunomide: a novel immunomodulatory agent. Arch Dermatol 136: 1204–1205Google Scholar
  12. Radford DJ, Savage CO, Nash GB (2000) Treatment of rolling neutrophils with antineutrophil cytoplasmic antibodies causes conversion to firm integrin-mediated adhesion. Arthritis Rheum 43: 1337–1345PubMedCrossRefGoogle Scholar
  13. Reinhold-Keller E, Beuge N, Latza U, de Groot K, Rudert K, Nolle B, Heller M, Gross WL (2000) An interdisciplinary approach to the care of patients with Wegener’s granulomatosis: long-term outcome in 155 patients. Arthritis Rheum 43: 1021–1032PubMedCrossRefGoogle Scholar
  14. Sibelius U, Hattar K, Schenkel A, Noll T, Csernok E, Gross WL, Mayet WJ, Piper HM, Seeger W, Grimminger F (1998) Wegener’s granulomatosis: anti-proteinase 3 antibodies are potent inductors of human endothelial cell signaling and leakage response. J Exp Med 187: 497–503PubMedCrossRefGoogle Scholar
  15. Siemasko KF, Chong AS, Williams JW, Bremer EG, Finnegan A (1996) Regulation of B cell function by the immunosuppressive agent leflunomide. Transplantation 61: 635–642PubMedCrossRefGoogle Scholar
  16. Stone JH, Uhlfelder ML, Hellmann DB, Crook S, Bedocs NM, Hoffman GS (2001) Etanercept combined with conventional treatment in Wegener’s granulomatosis: a six-month open-label trial to evaluate safety. Arthritis Rheum 44: 1149–1154PubMedCrossRefGoogle Scholar
  17. Talip F, Walker N, Khan W, Zimmermann B (2001) Treatment of Felty’s syndrome with leflunomide. J Rheumatol 28: 868–870PubMedGoogle Scholar
  18. Waldman WJ, Knight DA, Blinder L, Shen J, Lurain NS, Miller DM, Sedmak DD, Williams JW, Chong AS (1999) Inhibition of cytomegalovirus in vitro and in vivo by the experimental immunosuppressive agent leflunomide. Intervirology 42: 412–418PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2003

Authors and Affiliations

  • Angela Gause
    • 1
    • 2
  • Claudia Metzler
    • 1
  • Eva Reinhold-Keller
    • 1
  • Wolfgang L. Gross
    • 1
  1. 1.Poliklinik für RheumatologieUniversitätsklinikum Lübeck, Lübeck and Innere Medizin/Rheumatologie/Klinische Immunologie, Rheumaklinik Bad BramstedtBad BramstedtGermany
  2. 2.Poliklinik für RheumatologieUniversitätsklinikum LübeckLübeckFederal Republic of Germany

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