Leflunomide, a novel immunomodulator for the treatment of active rheumatoid arthritis

Clinical Therapeutics

Volumn 21, Issue 11, 1999, Pages 1837-1852

  Goldenberg, Marvin M ^a  

^a Managed Health Care Associates Inc   (United States)

Author keywords

Disease modifying antirheumatic drugs; Immunomodulator; Leflunomide; Rheumatoid arthritis

Indexed keywords

LEFLUNOMIDE; LIVER ENZYME; METHOTREXATE; PLACEBO; SALAZOSULFAPYRIDINE;

ALOPECIA; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; DRUG EFFICACY; DRUG ELIMINATION; DRUG MECHANISM; DRUG STRUCTURE; HUMAN; IMMUNOMODULATION; META ANALYSIS; REVIEW; RHEUMATOID ARTHRITIS;

EID: 0032763963     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/S0149-2918(00)86732-6     Document Type: Article

References (51)

1. 1. Lipsky PE. Rheumatoid arthritis. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, eds. Harrison's Principles of Internal Medicine. 14th ed. New York: McGraw-Hill; 1998:1880-1888.
2. 2. Mitchell DM, Spitz PW, Young DY, et al. Survival, prognosis, and causes of death in rheumatoid arthritis. Arthritis Rheum. 1986;29:706-714.
3. 3. Pincus T, Callahan LF, Sale WG, et al. Severe functional declines, work disability, and increased mortality in seventy-five rheumatoid arthritis patients studied over nine years. Arthritis Rheum. 1984;27:864-872.
4. 4. Leigh JP, Fries JF, Parikh N. Severity of disability and duration of disease in rheumatoid arthritis. J Rheumatol. 1992; 19:1906-1911.
5. 5. Eberhardt K, Larson B, Nived K. Early rheumatoid arthritis, some social, economic, and psychological aspects. Scand J Rheumatol. 1993;22:119-123.
6. 6. Yelin E, Callahan LF. The economic cost and social and psychological impact of musculoskeletal conditions. Arthritis Rheum. 1995;38:1351-1362.
7. 7. Lubeck DP. The economic impact of rheumatoid arthritis. In: Wolfe F, Pincus T, eds. Rheumatoid Arthritis: Pathogenesis, Assessment, Outcome, and Treatment. New York: Marcel Dekker; 1994:247-259.
8. 8. Bologna C, Viu P, Picot MC, et al. Longterm follow-up of 453 rheumatoid arthritis patients treated with methotrexate: An open retrospective, observational study. Br J Rheumatol. 1997;36:535-540.
9. 9. Ad Hoc Committee on Clinical Guidelines. Guidelines for RA management-ACR Clinical Guidelines Committee. Arthritis Rheum. 1996;39:713-722.
10. 10. Rau R, Herborn G, Menninger H, et al. Comparison of intramuscular methotrexate and gold sodium thiomalate in the treatment of early erosive rheumatoid arthritis: 12 month data of a double blind parallel study of 174 patients. Br J Rheumatol. 1997;36:345-352.
11. 11. Van Gestel AM, Haagsma CJ, Furst DE, et al. Treatment of early rheumatoid arthritis patients with slow acting antirheumatic drugs (SAARDS). Bailliere's Clin Rheumatol. 1997;11:65-82.
12. 12. Van der Heide A, Jacobs JW, Bijlsma JWJ, et al. The effectiveness of early treatment with "second-line" antirheumatic drugs. A randomized, controlled trial. Ann Intern Med. 1996;124:699-707.
13. 13. Egsmore C, Lund B, Borg G, et al. Patients with rheumatoid arthritis benefit from early 2nd line therapy: 5 year follow-up of a prospective double blind placebo controlled study. J Rheumatol. 1995;22:2208-2213.
14. 14. Pincus T. Long-term outcomes in rheumatoid arthritis. Br J Rheumatol. 1995;34 (Suppl 2):S59-S73.
15. 15. Mulherin D, Fitzgerald O, Bresnihan B. Clinical improvement and radiological deterioration in rheumatoid arthritis: Evidence that the pathogenesis of synovial inflammation and articular erosion may differ. Br J Rheumatol. 1996;35:1263-1268.
16. 16. Mottonen T, Paimela L, Ahonen J, et al. Outcomes in patients with early rheumatoid arthritis treated according to the saw-tooth strategy. Arthritis Rheum. 1996; 39:996-1005.
17. 17. Ten Wolde S, Breedveld FC, Aermans J, et al. Randomized, placebo controlled study of stopping second-line drugs in rheumatoid arthritis. Lancet. 1996;347:347-352.
18. 18. Ten Wolde S, Hermans J, Breedveld FC, et al. Effects of resumption of second line drugs in patients with rheumatoid arthritis that flared up after treatment discontinuation. Ann Rheum Dis. 1997;56:235-239.
19. 19. Wijnand MJH, van Piel PLCM. Management of adverse effects of disease-modifying antirheumatic drugs. Drug Saf. 1995;13:219-227.
20. 20. Greene S, Watanabe K, Braatz-Trulson J, et al. Inhibition of dihydroorotate dehydrogenase by the immunosuppressive agent leflunomide. Biochem Pharmacol. 1995;50:861-867.
21. 21. Fox RI. Mechanism of action of leflunomide in rheumatoid arthritis. J Rheumatol. 1998;25(Suppl 53):20-26.
22. 22. Xu X, Blinder L, Shen J, et al. In vivo mechanism by which leflunomide controls lymphoproliferative and autoimmune disease in MRL/MpJ-Ipr/pr mice. J Immunol. 1997;159:167-174.
23. 23. Silva HT, Cao W, Shorthouse R, et al. Mechanism of action of leflunomide: In vivo uridine administration reverses its inhibition of lymphocyte proliferation. Transplant Proc. 1996;28:3082-3084.
24. 24. Cao W, Kao P, Chao A, et al. Mechanism of the antiproliferative action of leflunomide. J Heart Lung Transplant. 1995;14: 1016-1030.
25. 25. Chong AS-F, Gebel H, Finnegan A, et al. Leflunomide, a novel immunomodulatory agent: In vitro analyses of the mechanism of immunosuppression. Transplant Proc. 1993;25:747-749.
26. 26. Kahan BD, Gibbons S, Tejpal N, et al. Synergistic interactions of cyclosporine and rapamycin to inhibit immune performances of normal human peripheral blood lymphocytes in vitro. Transplantation. 1991;51:232-239.
27. 27. Popovic S, Bartlett RR. The use of the murine graft versus host (CGVH) disease, a model for systemic lupus erythematosus (SLE) for drug discovery. Agents Actions. 1987;21:284-286.
28. 28. Gleichmann E, Elven EH, Veen JPW. A systemic lupus erythematosus (SLE)-like disease in mice induced by abnormal T-B cell cooperation. Preferential formation of autoantibodies characteristic of SLE. Eur J Immunol. 1982;12:152-159.
29. 29. Bartlett RR, Popovic S, Raiss RX. Development of autoimmunity in MRL/pr mice and the effect of drugs on this murine disease. Scand J Rheumatol. 1988;(75 Suppl):S290-S299.
30. 30. Bartlett RR, Schleyerbach R. Immunopharmacological profile of a novel isoxazol derivative, HWA 386, with potential antirheumatic activity. I. Disease modifying action on adjuvant arthritis of the rat. Int J Immunopharmacol. 1985;7:7-18.
31. 31. Pasternak RD, Wadopian NS, Wright P, et al. Disease modifying activity of HWA 486 in rat adjuvant-induced arthritis. Agents Actions. 1987;21:284-286.
32. 32. Hambleton P, McMahon S. Drug actions on delayed type hypersensitivity in rats with developing and established adjuvant arthritis. Agents Actions. 1990;29:338-342.
33. 33. McFarlin DE, Blank SF, Kibler RF, et al. Experimental allergic encephalomyelitis in the rat: Response to encephalitogenic proteins and peptide. Science. 1973;179: 478-480.
34. 34. Mokhtarian F, McFarlin DE, Raine CS. Adoptive transfer of myelin basic protein-sensitized T cells produces chronic relapsing demyelinating disease in mice. Nature. 1984;309:356-358.
35. 35. Lassman H, Suchanek G, Kitz K, et al. Antibodies in the pathogenesis of demyelination in chronic relapsing EAE (cr-EAE). In: Alvord EC, Kies MW, Suckling AJ, eds. Experimental Allergic Encephalomyelitis: A Useful Model for Multiple Sclerosis. New York: Alan R. Liss Inc; 1984:3-5.
36. 36. Smith ME, Eller NL, McFarland HF, et al. Age dependence of clinical and pathological manifestations of autoimmune demyelination: Implications for multiple sclerosis. Am J Pathol. 1999;155:1147-1161.
37. 37. Bartlett RR, Mattar T, Neithmann U, et al. Leflunomide (HWA 486): A novel immunorestoring drug. In: Lewis AJ, Doherty NS, Ackermann NR, eds. Therapeutic Approaches to Inflammatory Diseases. New York: Elsevier Science; 1989:215-228.
38. 38. Thoenes GH, Umscheid T, Sitter T, et al. Cyclosporin A inhibits autoimmune experimental tubulointerstitial nephritis. Immunol Lett. 1987;15:301-306.
39. 39. Williams JW, Xiao F, Foster PF, et al. Immunosuppressive effects of leflunomide in cardiac allograft model. Transplant Proc. 1993;25:745-746.
40. 40. Leflunomide [package insert]. Kansas City, Mo: Hoechst Marion Roussel; 1998.
41. 41. United States Food and Drug Administration. Summary Basis of Approval, Leflunomide: NDA 20-905. Washington, DC: United States Department of Health and Human Services; 1997.
42. 42. Mladenovic V, Dornljan Z, Rozman B, et al. Safety and effectiveness of leflunomide in the treatment of patients with active rheumatoid arthritis. Arthritis Rheum. 1995;38:1595-1603.
43. 43. Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1965;8:302-334.
44. 44. Rozman B. Clinical experience with leflunomide in rheumatoid arthritis. J Rheumatol. 1998;25(Suppl 53):27-32.
45. 45. Paulus HE, Egger MJ, Ward JR, et al. Analysis of improvement in individual rheumatoid arthritis patients treated with disease-modifying antirheumatic drugs, based on the findings in patients treated with placebo. Arthritis Rheum. 1990;33:477-484.
46. 46. Smolen S, Kalden JR, Scott DL, et al. Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: A double-blind, randomized, multicentre trial. Lancet. 1999; 353:259-266.
47. 47. Smolen JS, Kalden JR, Rozman B, et al. A double-blind, randomized, phase III trial of leflunomide vs placebo vs sulfasalazine in rheumatoid arthritis. Arthritis Rheum. 1998;41(Suppl):594. Abstract.
48. 48. Weaver A, Caldwell J, Olsen N, et al. Treatment of active rheumatoid arthritis with leflunomide compared to placebo or methotrexate. Arthritis Rheum. 1998;41 (Suppl):593. Abstract.
49. 49. Tugwell P, Bombardier C, Strand V, et al. Treatment of active rheumatoid arthritis with leflunomide improves functional activities and health related quality of life (HRQOL). Arthritis Rheum. 1998;41 (Suppl):732. Abstract.
50. 50. Schiff M, Kaine J, Sharp J, et al. X-ray analysis of 12 months treatment of active rheumatoid arthritis with leflunomide compared to placebo or methotrexate. Arthritis Rheum. 1998;41(Suppl):736. Abstract.
51. 51. Weinblatt ME, Kremer JM, Coblyn JS, et al. Combination therapy with leflunomide-methotrexate in refractory rheumatoid arthritis. In: Program and abstracts of the Annual Meeting of the European League Against Rheumatoid Arthritis; September 5-8, 1998; Geneva, Switzerland. Abstract 156.