Abstract
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▴ Tacrolimus, a hydrophobic macrolide with immu-nosuppressant properties, has recently been evaluated as a new treatment for adults with active rheumatoid arthritis.
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▴ Oral tacrolimus 3mg once daily was significantly more effective than placebo in patients with rheumatoid arthritis (RA) who were refractory or intolerant to disease-modifying antirheumatic drugs (DMARDs), according to results from a 6-month, phase III trial; American College of Rheumatology 20 (ACR20) response rates were 27% and 10%. Tacrolimus 3mg once daily was effective in the same patient group in a 12-month, open-label trial; the ACR20 response rate was 38%.
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▴ Oral tacrolimus 3mg once daily was effective in combination with established methotrexate therapy in patients with RA in a 6-month, open-label trial. The ACR20 response rate was 53%.
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▴ Oral tacrolimus 3mg once daily was generally well tolerated by patients with active RA refractory or intolerant to previous DMARD treatment or when administered as combination therapy in patients with RA on established methotrexate therapy.
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References
American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 update. Arthritis Rheum 2002 Feb; 46(2): 328–46
Feldmann M, Brennan FM, Maini RN. Role of cytokines in rheumatoid arthritis. Annu Rev Immunol 1996; 14: 397–440
Scott LJ, McKeage K, Keam SJ, et al. Tacrolimus: a further update of its use in the management of organ transplantation. Drugs 2003; 63(12): 1247–97
Cheer SM, Plosker GL. Tacrolimus ointment: a review of its therapeutic potential as a topical therapy in atopic dermatitis. Am J Clin Dermatol 2001; 2(6): 389–406
Staatz CE, Tett SE. Clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ transplantation. Clin Pharmacokinet 2004; 43(10): 623–53
Miyata S, Ohkubo Y, Mutoh S. A review of the action of tacrolimus (FK506) on experimental models of rheumatoid arthritis. Inflamm Res 2005 Jan; 54(1): 1–9
Fujisawa Canada. Prograf® (tacrolimus injection and capsule): product monograph. Markham (ON): Fujisawa Canada, 2004 Feb
Tocci MJ, Matkovich DA, Collier KA, et al. The immunosup-pressant FK506 selectively inhibits expression of early T cell activation genes. J Immunol 1989 Jul 15; 143(2): 718–26
Sawada S, Suzuki G, Kawase Y, et al. Novel immunosuppressive agent, FK506: in vitro effects on the cloned T cell activation. J Immunol 1987 Sep 15; 139(6): 1797–803
Sakuma S, Kato Y, Nishigaki F, et al. FK506 potently inhibits T cell activation induced TNF-α and IL-1β production in vitro by human peripheral blood mononuclear cells. Br J Pharmacol 2000 Aug; 130(7): 1655–63
Sakuma S, Kato Y, Nishigaki F, et al. Effects of FK506 and other immunosuppressive anti-rheumatic agents on T cell activation mediated IL-6 and IgM production in vitro. Int Immunopharmacol 2001 Apr; 1(4): 749–57
Magari K, Miyata S, Nishigaki F, et al. Differential effects of FK506 and methotrexate on inflammatory cytokine levels in rat adjuvant-induced arthritis. J Rheumatol 2003 Oct; 30(10): 2193–200
Magari K, Nishigaki F, Sasakawa T, et al. Anti-arthritic properties of FK506 on collagen-induced arthritis in rats. Inflamm Res 2003 Dec; 52(12): 524–9
Fuseler JW, Hearth-Holmes M, Grisham MB, et al. FK506 attenuates developing and established joint inflammation and suppresses interleukin 6 and nitric oxide expression in bacterial cell wall induced polyarthritis. J Rheumatol 2000 Jan; 27(1): 190–9
Sugiyama E, Suzuki H, Tunru IS, et al. FK506, an immunosup-pressant, partially inhibits interleukin 6 production by adherent rheumatoid synovial cells. J Rheumatol 1994 Sep; 21: 1597–601
Inamura N, Hashimoto M, Nakahara K, et al. Immunosuppressive effect of FK506 on collagen-induced arthritis in rats. Clin Immunol Immunopathol 1988 Jan; 46(1): 82–90
Takaoka Y, Nagai H, Tanahashi M, et al. Cyclosporin A and FK-506 inhibit development of superantigen-potentiated collagen-induced arthritis in mice. Gen Pharmacol 1998 May; 30(5): 777–82
Sakuma S, Nishigaki F, Magari K, et al. FK506 is superior to methotrexate in therapeutic effects on advanced stage of rat adjuvant-induced arthritis. Inflamm Res 2001 Oct; 50(10): 509–14
Magari K, Miyata S, Nishigaki F, et al. Comparison of antiarthritic properties of leflunomide with methotrexate and FK506: effect on T cell activation-induced inflammatory cytokine production in vitro and rat adjuvant-induced arthritis. Inflamm Res 2004 Oct; 53(10): 544–50
Magari K, Miyata S, Ohkubo Y, et al. Calcineurin inhibitors exert rapid reduction of inflammatory pain in rat adjuvant-induced arthritis. Br J Pharmacol 2003 Jul; 139(5): 927–34
Nishigaki F, Sakuma S, Ogawa T, et al. FK506 induces chondrogenic differentiation of clonal mouse embryonic carcinoma cells, ATDC 5. Eur J Pharmacol 2002 Feb 22; 437(3): 123–8
Tang L, Ebara S, Kawasaki S, et al. FK506 enhanced osteoblastic differentiation in mesenchymal cells. Cell Biol Int 2002; 26(1): 75–84
Voggenreiter G, Assenmacher S, Kreuzfelder E, et al. Immunosuppression with FK506 increases bone induction in demineralized isogeneic and xenogeneic bone matrix in the rat. J Bone Miner Res 2000 Sep; 15(9): 1825–34
Yocum DE, Furst DE, Bensen WG, et al. Safety of tacrolimus in patients with rheumatoid arthritis: long-term experience. Rheumatology (Oxford) 2004 Aug; 43(8): 992–9
Kremer JM, Habros JS, Kolba KS, et al. Tacrolimus in rheumatoid arthritis patients receiving concomitant methotrexate: a six-month, open-label study. Arthritis Rheum 2003 Oct; 48(10): 2763–8
Wallemacq PE, Verbeeck RK. Comparative clinical pharmacokinetics of tacrolimus in paediatric and adult patients. Clin Pharmacokinet 2001; 40(4): 283–95
Fujisawa. Prograf®: prescribing information (US) [online]. Available from URL: http://www.fujisawa.com [Accessed 2003 Aug 10]
Holum MB, Wisemandle W, Bekersky I. Concomitant tacrolimus (TAC) and methotrexate (MTX) pharmacokinetics (PK) in rheumatoid arthritis (RA) patients. J Clin Pharmacol 2002 Sep; 42(9): 1053
Kondo H, Abe T, Hashimoto H, et al. Efficacy and safety of tacrolimus (FK506) in treatment of rheumatoid arthritis: a randomized, double blind, placebo controlled dose-finding study. J Rheumatol 2004 Feb; 31(2): 243–51
Furst DE, Saag K, Fleischmann MR, et al. Efficacy of tacrolimus in rheumatoid arthritis patients who have been treated unsuccessfully with methotrexate: a six-month, double-blind, randomized, dose-ranging study. Arthritis Rheum 2002 Aug; 46(8): 2020–8
Yocum DE, Furst DE, Kaine JL, et al. Efficacy and safety of tacrolimus in patients with rheumatoid arthritis: a double-blind trial. Arthritis Rheum 2003 Dec; 48(12): 3328–37
Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988 Mar; 31(3): 315–24
Hochberg MC, Chang RW, Dwosh I, et al. The American College of Rheumatology 1991 revised criteria for the classification of global functional status in rheumatoid arthritis. Arthritis Rheum 1992 May; 35(5): 498-502
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Curran, M.P., Perry, C.M. Tacrolimus. CNS Drugs 65, 993–1001 (2005). https://doi.org/10.2165/00003495-200565070-00005
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DOI: https://doi.org/10.2165/00003495-200565070-00005