Skip to main content
SpringerLink
Log in

Leflunomide

  • Chapter
Antirheumatic Therapy: Actions and Outcomes

Part of the book series: Progress in Inflammation Research ((PIR))

  • 689 Accesses

Abstract

Leflunomide (HWA486) is a small molecule disease-modifying anti-rheumatic drug (DMARD) developed in the mid 1980s and 90s. It is structurally unrelated to other currently available immunomodulatory agents and was first evaluated in experimental models of autoimmune disease and post-transplant graft versus host disease. Its action as an anti-inflammatory and immunomodulatory drug has been applied to the treatment of rheumatoid arthritis (RA) in both in vitro and in vivo studies. A number of well-conducted randomised controlled studies led to its approval for the treatment of RA in the late 1990s. Leflunomide is effective in improving symptoms of RA and prevention of radiographic erosions. Like methotrexate or sulfasalazine, which are two commonly used first-line DMARDs, leflunomide has been shown to improve function and quality of life in patients with active RA.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Xu X, Blinder L, Shen J, Gong H, Finnegan A, Williams JW, Chong AS (1997) In vivo mechanism by which leflunomide controls lymphoproliferative and autoimmune disease in MRL/MpJ-lpr/lpr mice. J Immunol 159: 167–174

    CAS  PubMed  Google Scholar 

  2. Lang R, Wagner H, Heeg K (1995) Differential effects of the immunosuppressive agents cyclosporine and leflunomide in vivo. Leflunomide blocks clonal T cell expansion yet allows production of lymphokines and manifestation of T cell-mediated shock. Transplantation 59: 382–389

    CAS  PubMed  Google Scholar 

  3. Zielinski T, Zeitter D, Muller S, Bartlett RR (1995) Leflunomide, a reversible inhibitor of pyrimidine biosynthesis? Inflamm Res 44 (Suppl 2): S207–S208

    Article  CAS  PubMed  Google Scholar 

  4. Cao WW, Kao PN, Chao AC, Gardner P, Ng J, Morris RE (1995) 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 14: 1016–1030

    CAS  PubMed  Google Scholar 

  5. Siemasko KF, Chong AS, Williams JW, Bremer EG, Finnegan A (1996) Regulation of B cell function by the immunosuppressive agent leflunomide. Transplantation 61: 635–642

    Article  CAS  PubMed  Google Scholar 

  6. Chong AS, Rezai K, Gebel HM, Finnegan A, Foster P, Xu X, Williams JW (1996) Effects of leflunomide and other immunosuppressive agents on T cell proliferation in vitro. Transplantation 61: 140–145

    Article  CAS  PubMed  Google Scholar 

  7. Cherwinski HM, Cohn RG, Cheung P, Webster DJ, Xu YZ, Caulfield JP, Young JM, Nakano G, Ransom JT (1995) The immunosuppressant leflunomide inhibits lympho cyte proliferation by inhibiting pyrimidine biosynthesis. J Pharmacol Exp Ther 275: 1043–1049

    CAS  PubMed  Google Scholar 

  8. Fairbanks LD, Bofill M, Ruckemann K, Simmonds HA (1995) Importance of ribonu cleotide availability to proliferating T-lymphocytes from healthy humans. Dispropor tionate expansion of pyrimidine pools and contrasting effects of de novo synthesis inhibitors. J Biol Chem 270: 29682–29689

    Article  CAS  PubMed  Google Scholar 

  9. Greene S, Watanabe K, Braatz-Trulson J, Lou L (1995) Inhibition of dihydroorotate dehydrogenase by the immunosuppressive agent leflunomide. Biochem Pharmacol 50: 861–867

    Article  CAS  PubMed  Google Scholar 

  10. Elder RT, Xu X, Williams JW, Gong H, Finnegan A, Chong AS (1997) The immuno suppressive metabolite of leflunomide, A77 1726, affects murine T cells through two biochemical mechanisms. J Immunol 159: 22–27

    CAS  PubMed  Google Scholar 

  11. Xu X, Williams JW, Gong H, Finnegan A, Chong AS (1996) Two activities of the immunosuppressive metabolite of leflunomide, A77 1726. Inhibition of pyrimidine nucleotide synthesis and protein tyrosine phosphorylation. Biochem Pharmacol 52: 527–534

    Article  CAS  PubMed  Google Scholar 

  12. Davis JP, Cain GA, Pitts WJ, Magolda RL, Copeland RA (1996) The immunosuppres-sive metabolite of leflunomide is a potent inhibitor of human dihydroorotate dehydro-genase. Biochemistry 35: 1270–1273

    Article  CAS  PubMed  Google Scholar 

  13. Cherwinski HM, Byars N, Ballaron SJ, Nakano GM, Young JM, Ransom JT (1995) Leflunomide interferes with pyrimidine nucleotide biosynthesis. Inflamm Res 44: 317–322

    Article  CAS  PubMed  Google Scholar 

  14. Silva HT Jr., Cao W, Shorthouse RA, Loffler M, Morris RE (1997) In vitro and in vivo effects of leflunomide, brequinar, and cyclosporine on pyrimidine biosynthesis. Trans plant Proc 29: 1292–1293

    CAS  Google Scholar 

  15. Williamson RA, Yea CM, Robson PA, Curnock AP, Gadher S, Hambleton AB, Woodward K, Bruneau JM, Hambleton P, Moss D et al (1995) Dihydroorotate dehydrogenase is a high affinity binding protein for A77 1726 and mediator of a range of biological effects of the immunomodulatory compound. J Biol Chem 270: 22467–22472

    Article  CAS  PubMed  Google Scholar 

  16. Kuo EA, Hambleton PT, Kay DP, Evans PL, Matharu SS, Little E, McDowall N, Jones CB, Hedgecock CJ, Yea CM et al (1996) Synthesis, structure-activity relationships, and pharmacokinetic properties of dihydroorotate dehydrogenase inhibitors: 2-cyano-3-cyclopropyl-3-hydroxy-N-[3′-methyl-4′-(trifluoromethyl) phenyl] propenamide and related compounds. J Med Chem 39: 4608–4621

    Article  CAS  PubMed  Google Scholar 

  17. Fox RI, Herrmann ML, Frangou CG, Wahl GM, Morris RE, Strand V, Kirschbaum BJ (1999) Mechanism of action for leflunomide in rheumatoid arthritis. Clin Immunol 93: 198–208

    Article  CAS  PubMed  Google Scholar 

  18. Fairbanks LD, Ruckemann K, Qiu Y, Hawrylowicz CM, Richards DF, Swaminathan R, Kirschbaum B, Simmonds HA (1999) Methotrexate inhibits the first committed step of purine biosynthesis in mitogen-stimulated human T-lymphocytes: A metabolic basis for efficacy in rheumatoid arthritis? Biochem J 342 (Pt 1): 143–152

    Article  CAS  PubMed  Google Scholar 

  19. Bartlett RR (1986) Immunopharmacological profile of HWA 486, a novel isoxazol derivative — II. In vivo immunomodulating effects differ from those of cyclophosphamide, prednisolone, or cyclosporin A. Int J Immunopharmacol 8: 199–204

    Article  CAS  PubMed  Google Scholar 

  20. Xu X, Williams JW, Bremer EG, Finnegan A, Chong AS (1995) Inhibition of protein tyrosine phosphorylation in T cells by a novel immunosuppressive agent, leflunomide. J Biol Chem 270: 12398–12403

    Article  CAS  PubMed  Google Scholar 

  21. Manna SK, Aggarwal BB (1999) Immunosuppressive leflunomide metabolite (A77 1726) blocks TNF-dependent nuclear factor-kappa B activation and gene expression. J Immunol 162: 2095–2102

    CAS  PubMed  Google Scholar 

  22. Cutolo M, Sulli A, Ghiorzo P, Pizzorni C, Craviotto C, Villaggio B (2003) Anti-inflam matory effects of leflunomide on cultured synovial macrophages from patients with rheumatoid arthritis. Ann Rheum Dis 62: 297–302

    Article  CAS  PubMed  Google Scholar 

  23. Cao WW, Kao PN, Aoki Y, Xu JC, Shorthouse RA, Morris RE (1996) A novel mechanism of action of the immunomodulatory drug, leflunomide: augmentation of the immunosuppressive cytokine, TGF-beta 1, and suppression of the immunostimulatory cytokine, IL-2. Transplant Proc 28: 3079–3080

    CAS  PubMed  Google Scholar 

  24. Hamilton LC, Vojnovic I, Warner TD (1999) A771726, the active metabolite of leflunomide, directly inhibits the activity of cyclo-oxygenase-2 in vitro and in vivo in a substrate-sensitive manner. Br J Pharmacol 127: 1589–1596

    Article  CAS  PubMed  Google Scholar 

  25. Dimitrijevic M, Bartlett RR (1996) Leflunomide, a novel immunomodulating drug, inhibits homotypic adhesion of mononuclear cells in rheumatoid arthritis. Transplant Proc 28: 3086–3087

    CAS  PubMed  Google Scholar 

  26. Kraan MC, de Koster BM, Elferink JG, Post WJ, Breedveld FC, Tak PP (2000) Inhibition of neutrophil migration soon after initiation of treatment with leflunomide or methotrexate in patients with rheumatoid arthritis: findings in a prospective, randomized, double-blind clinical trial in fifteen patients. Arthritis Rheum 43: 1488–1495

    Article  CAS  PubMed  Google Scholar 

  27. Kraan MC, Reece RJ, Barg EC, Smeets TJ, 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: 1820–1830

    Article  CAS  PubMed  Google Scholar 

  28. Deage V, Burger D, Dayer JM (1998) Exposure of T lymphocytes to leflunomide but not to dexamethasone favours the production by monocytic cells of interleukin-1 receptor antagonist and the tissue-inhibitor of metalloproteinases-1 over that of interleukin-1 beta and metalloproteinases. Eur Cytokine Netw 9: 663–668

    CAS  PubMed  Google Scholar 

  29. Ho CY, Wong CKs, Li EK, Tarn LS, Lam CW (2003) Suppressive effect of combination treatment of leflunomide and methotrexate on chemokine expression in patients with rheumatoid arthritis. Clin Exp Immunol 133: 132–138

    Article  CAS  PubMed  Google Scholar 

  30. Rozman B (2002) Clinical pharmacokinetics of leflunomide. Clin Pharmacokinet 41: 421–30

    Article  CAS  PubMed  Google Scholar 

  31. Beaman JM, Hackett LP, Luxton G, Illett KF (2002) Effect of hemodialysis on leflunomide plasma concentrations. Ann Pharmacother 36: 75–77

    Article  PubMed  Google Scholar 

  32. Jakez-Ocampo J, Richaud-Patin Y, Simon JA, Llorente L (2002) Weekly dose of leflunomide for the treatment of refractory rheumatoid arthritis: An open pilot comparative study. Joint Bone Spine 69: 307–311

    Article  PubMed  Google Scholar 

  33. Osiri M, Shea B, Robinson V, Suarez-Almazor M, Strand V, Tugwell P, Wells G (2003) Leflunomide for the treatment of rheumatoid arthritis: a systematic review and metaanalysis J Rheumatol 30: 1182–1190

    CAS  PubMed  Google Scholar 

  34. Smolen JS, Kalden JR, Scott DL, Rozman B, Kvien TK, Larsen A, Loew-Friedrich I, Oed C, Rosenburg R (1999) Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. European Leflunomide Study Group. Lancet 353: 259–266

    Article  CAS  PubMed  Google Scholar 

  35. Strand V, Cohen S, Schiff M, Weaver A, Fleischmann R, Cannon G, Fox R, Moreland L, Olsen N, Fürst D et al (1999) Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Leflunomide Rheumatoid Arthritis Investigators Group. Arch Intern Med 159: 2542–2550

    Article  CAS  PubMed  Google Scholar 

  36. Emery P, Breedveld FC, Lemmel EM, Kaltwasser JP, Dawes PT, Gomor B, Van Den Bosch F, Nordstrom D, Bjorneboe O, Dahl R et al (2000) A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis. Rheumatology (Oxford) 39: 655–665

    Article  CAS  Google Scholar 

  37. Scott DL, Smolen JS, Kalden JR, van de Putte LB, Larsen A, Kvien TK, Schattenkirchner M, Nash P, Oed C, Loew-Friedrich I et al (2001) Treatment of active rheumatoid arthritis with leflunomide: Two year follow up of a double blind, placebo controlled trial versus sulfasalazine. Ann Rheum Dis 60: 913–923

    Article  CAS  PubMed  Google Scholar 

  38. Cohen S, Cannon GW, Schiff M, Weaver A, Fox R, Olsen N, Fürst D, Sharp J, Moreland L, Caldwell J et al (2001) Two-year, blinded, randomized, controlled trial of treatment of active rheumatoid arthritis with leflunomide compared with methotrexate. Utilization of Leflunomide in the Treatment of Rheumatoid Arthritis Trial Investigator Group. Arthritis Rheum 44: 1984–1992

    Article  CAS  PubMed  Google Scholar 

  39. Kalden JR, Schattenkirchner M, Sorensen H, Emery P, Deighton C, Rozman B, Breedveld F (2003) The efficacy and safety of leflunomide in patients with active rheumatoid arthritis: A five-year follow up study. Arthritis Rheum 48: 1513–1520

    Article  CAS  PubMed  Google Scholar 

  40. Pincus T, Callahan LF, Brooks RH, Fuchs HA, Olsen NJ, Kaye JJ (1989) Self-report questionnaire scores in rheumatoid arthritis compared with traditional physical, radiographic, and laboratory measures. Ann Intern Med 110: 259–266

    CAS  PubMed  Google Scholar 

  41. Callahan LF, Pincus T, Huston JW, 3rd, Brooks RH, Nance EP, Jr., Kaye JJ (1997) Mea sures of activity and damage in rheumatoid arthritis: depiction of changes and prediction of mortality over five years. Arthritis Care Res 10: 381–394

    Article  CAS  PubMed  Google Scholar 

  42. Kalden JR, Scott DL, Smolen JS, Schattenkirchner M, Rozman B, Williams BD, Kvien TK, Jones P, Williams RB, Oed C et al (2001) Improved functional ability in patients with rheumatoid arthritis — longterm treatment with leflunomide versus sulfasalazine. European Leflunomide Study Group. J Rheumatol 28: 1983–1991

    CAS  PubMed  Google Scholar 

  43. Wells GA, Tugwell P, Kraag GR, Baker PR, Groh J, Redelmeier DA (1993) Minimum important difference between patients with rheumatoid arthritis: The patient’s perspec tive. J Rheumatol 20: 557–560

    CAS  PubMed  Google Scholar 

  44. Kosinski M, Zhao SZ, Dedhiya S, Osterhaus JT, Ware JE Jr (2000) Determining mini mally important changes in generic and disease-specific health-related quality of life questionnaires in clinical trials of rheumatoid arthritis. Arthritis Rheum 43: 1478–1487

    Article  CAS  PubMed  Google Scholar 

  45. Redelmeier DA, Lorig K (1993) Assessing the clinical importance of symptomatic improvements. An illustration in rheumatology. Arch Intern Med 153: 1337–1342

    Article  CAS  PubMed  Google Scholar 

  46. Talamo J, Frater A, Gallivan S, Young A (1997) Use of the short form 36 (SF36) for health status measurement in rheumatoid arthritis. Br J Rheumatol 36: 463–469

    Article  CAS  PubMed  Google Scholar 

  47. Sharp JT, Strand V, Leung H, Hurley F, Loew-Friedrich I (2000) Treatment with lefluno mide slows radiographic progression of rheumatoid arthritis: Results from three ran domized controlled trials of leflunomide in patients with active rheumatoid arthritis Leflunomide Rheumatoid Arthritis Investigators Group. Arthritis Rheum 43: 495–505

    Article  CAS  PubMed  Google Scholar 

  48. Larsen A, Kvien TK, Schattenkirchner M, Rau R, Scott DL, Smolen JS, Rozman B, West-hovens R, Tikly M, Oed C et al (2001) Slowing of disease progression in rheumatoid arthritis patients during long-term treatment with leflunomide or sulfasalazine. Scand J Rheumatol 30: 135–142

    Article  CAS  PubMed  Google Scholar 

  49. Reece RJ, Kraan MC, Radjenovic A, Veale DJ, O’Connor PJ, Ridgway JP, Gibbon WW, Breedveld FC, Tak PP, Emery P (2002) Comparative assessment of leflunomide and methotrexate for the treatment of rheumatoid arthritis, by dynamic enhanced magnetic resonance imaging. Arthritis Rheum 46: 366–372

    Article  CAS  PubMed  Google Scholar 

  50. Kremer JM, Genovese MC, Cannon GW, Caldwell JR, Cush JJ, Fürst DE, Luggen ME, Keystone E, Weisman MH, Bensen WM et al (2002) Concomitant leflunomide therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 137: 726–733

    CAS  PubMed  Google Scholar 

  51. Kiely PD, Johnson DM (2002) Infliximab and leflunomide combination therapy in rheumatoid arthritis: An open-label study. Rheumatology (Oxford) 41: 631–637

    Article  CAS  Google Scholar 

  52. Reich K, Hummel KM, Beckmann I, Mossner R, Neumann C (2002) Treatment of severe psoriasis and psoriatic arthritis with leflunomide. Br J Dermatol 146: 335–336

    Article  CAS  PubMed  Google Scholar 

  53. Cuchacovich M, Soto L (2002) Leflunomide decreases joint erosions and induces reparative changes in a patient with psoriatic arthritis. Ann Rheum Dis 61: 942–943

    Article  CAS  PubMed  Google Scholar 

  54. Kaltwasser JP, Nash P, Gladman D, Mease P (2002) Efficacy and Safety of Leflunomide in the treatment of psoriatic arthritis: Results from the TOPAS study, American College of Rheumatology 66th Annual Scientific Meeting, New Orleans, Louisiana

    Google Scholar 

  55. Popovic S, Bartlett RR (1986) Disease modifying activity of HWA 486 on the development of SLE in MRL/l-mice. Agents Actions 19: 313–314

    Article  CAS  PubMed  Google Scholar 

  56. Popovic S, Bartlett RR (1987) The use of the murine chronic graft versus host (CGVH) disease, a model for systemic lupus erythematosus (SLE), for drug discovery. Agents Actions 21: 284–286

    Article  CAS  PubMed  Google Scholar 

  57. Vidic-Dankovic B, Kosec D, Damjanovic M, Apostolski S, Isakovic K, Bartlett RR (1995) Leflunomide prevents the development of experimentally induced myasthenia gravis. Int J Immunopharmacol 17: 273–281

    Article  CAS  PubMed  Google Scholar 

  58. Bartlett RR, Anagnostopulos H, Zielinski T, Mattar T, Schleyerbach R (1993) Effects of leflunomide on immune responses and models of inflammation. Springer Semin Immunopathol 14: 381–394

    Article  CAS  PubMed  Google Scholar 

  59. Remer CF, Weisman MH, Wallace DJ (2001) Benefits of leflunomide in systemic lupus erythematosus: A pilot observational study. Lupus 10: 480–483

    Article  CAS  PubMed  Google Scholar 

  60. Williams JW, Xiao F, Foster PF, Chong A, Sharma S, Bartlett R, Sankary HN (1993) Immunosuppressive effects of leflunomide in a cardiac allograft model. Transplant Proc 25: 745–746

    CAS  PubMed  Google Scholar 

  61. Kuchle CC, Thoenes GH, Langer KH, Schorlemmer HU, Bartlett RR, Schleyerbach R (1991) Prevention of kidney and skin graft rejection in rats by leflunomide, a new immunomodulating agent. Transplant Proc 23: 1083–1086

    CAS  PubMed  Google Scholar 

  62. Talip F, Walker N, Khan W, Zimmermann B (2001) Treatment of Felty’s syndrome with leflunomide. J Rheumatol 28: 868–870

    CAS  PubMed  Google Scholar 

  63. Haberhauer G, Kittl EM, Dunky A, Feyertag J, Bauer K (2001) Beneficial effects of leflunomide in glucocorticoid-and methotrexate-resistant Takayasu’s arteritis. Clin Exp Rheumatol 19: 477–478

    CAS  PubMed  Google Scholar 

  64. Majithia V, Sanders S, Harisdangkul V, Wilson JG (2003) Successful treatment of sarcoidosis with leflunomide. Rheumatology (Oxford) 42: 700–702

    Article  CAS  Google Scholar 

  65. Breedveld FC, Dayer JM (2000) Leflunomide: mode of action in the treatment of rheumatoid arthritis. Ann Rheum Dis 59: 841–849

    Article  CAS  PubMed  Google Scholar 

  66. Auer J, Hinterreiter M, Allinger S, Kirchgatterer A, Knoflach P (2000) Severe pancytopenia after leflunomide in rheumatoid arthritis. Acta Med Austriaca 27: 131–132

    Article  CAS  PubMed  Google Scholar 

  67. Hill RL, Topliss DJ, Purcell PM (2003) Pancytopenia associated with leflunomide and methotrexate. Ann Pharmacother 37: 149

    Article  PubMed  Google Scholar 

  68. Mladenovic V, Domljan Z, Rozman B, Jajic I, Mihajlovic D, Dordevic J, Popovic M, Dimitrijevic M, Zivkovic M, Campion G et al (1995) 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 38: 1595–1603

    Article  CAS  PubMed  Google Scholar 

  69. Rozman B (1998) Clinical experience with leflunomide in rheumatoid arthritis. Leflunomide Investigators’ Group. J Rheumatol (Suppl) 53: 27–32

    CAS  Google Scholar 

  70. Coblyn JS, Shadick N, Helfgott S (2001) Leflunomide-associated weight loss in rheumatoi arthritis. Arthritis Rheum 44: 1048–1051

    Article  CAS  PubMed  Google Scholar 

  71. Weinblatt ME, Kremer JM, Coblyn JS, Maier AL, Helfgott SM, Morrell M, Byrne VM, Kaymakcian MV, Strand V (1999) Pharmacokinetics, safety, and efficacy of combination treatment with methotrexate and leflunomide in patients with active rheumatoid arthritis. Arthritis Rheum 42: 1322–1328

    Article  CAS  PubMed  Google Scholar 

  72. Hoi A, Littlejohn GO (2003) Aminotransferase levels during treatment of rheumatoid arthritis with leflunomide in clinical practice. Ann Rheum Dis 62: 379

    Article  CAS  PubMed  Google Scholar 

  73. Prokopowitsch AS, Diogenes AHM, Borges CT, Torigoe D, Kochen J, Laurindo IMM (2002) Leflunomide induces progressive increase in rheumatoid arthritis lipid profile, American College of Rheumatology 66th Annual Scientific Meeting, New Orleans, Louisiana

    Google Scholar 

  74. Kaplan MJ (2001) Leflunomide Aventis Pharma. Curr Opin Investig Drugs 2: 222–230

    CAS  PubMed  Google Scholar 

  75. Chakravarty EF, Sanchez-Yamamoto D, Bush TM (2003) The use of disease modifying antirheumatic drugs in women with rheumatoid arthritis of childbearing age: a survey of practice patterns and pregnancy outcomes. J Rheumatol 30: 241–246

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre for Inflammatory Disease, Monash University, Monash Medical Centre, Melbourne, Australia

    Alberta Hoi

  2. Department of Rheumatology, Monash Medical Centre, 246 Clayton Rd, Clayton, Melbourne, Victoria, 3168, Australia

    Geoffrey Littlejohn

Authors
  1. Alberta Hoi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Geoffrey Littlejohn
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Clinical Pharmacology and Toxicology, St. Vincent’s Hospital Sydney, Victoria Street Darlinghurst, Sydney, NSW, 2010, Australia

    Richard O. Day

  2. 546 Dept. of Rheumatology, University Hospital Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands

    Piet L. C. M. van Riel

  3. Carl M.Pearson Professor of Rheumatology, 1000 Veteran Ave Rm 32-59, Los Angeles, CA, 90025-1670, USA

    Daniel E. FĂĽrst

  4. Department of Rheumatology, St Vicent’s University Hospital, Elm Park, Dublin 4, Ireland

    Barry Bresnihan

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Birkhäuser Verlag Basel/Switzerland

About this chapter

Cite this chapter

Hoi, A., Littlejohn, G. (2005). Leflunomide. In: Day, R.O., Fürst, D.E., van Riel, P.L.C.M., Bresnihan, B. (eds) Antirheumatic Therapy: Actions and Outcomes. Progress in Inflammation Research. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-7726-7_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-7643-7726-7_10

  • Publisher Name: Birkhäuser Basel

  • Print ISBN: 978-3-7643-6595-0

  • Online ISBN: 978-3-7643-7726-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation