Abstract
The aim of this study was to assess if low-dose tacrolimus is efficacious for the treatment of rheumatoid arthritis (RA) when combined with methotrexate (MTX). The clinical courses of 32 RA patients who received tacrolimus plus MTX were analyzed retrospectively. Disease activity and clinical response were evaluated by DAS28 (disease activity score of 28 joints) and EULAR (European League Against Rheumatism) response criteria. Tacrolimus was started at 1 mg/day in five patients, 1.5 mg/day in 24 patients, and three mg/day in 3 patients. At six months, tacrolimus was continued at 1–2 mg/day in 27 of 32 patients, but was discontinued in five cases who showed no or inadequate response. Of the 32 patients, 47% were evaluated as having a moderate or good response at one month of tacrolimus therapy, and 72% at six months. No serious adverse events were observed. Our results suggest that the addition of tacrolimus at low dose to MTX for the treatment of patients with moderately active RA appears to be highly efficacious. Further studies are required for the appropriate use of this expensive immunosuppressant in the treatment of RA.
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References
Kitahara K, Kawai S. Cyclosporine and tacrolimus for the treatment of rheumatoid arthritis. Curr Opin Rheumatol. 2007;19:238–45.
Kondo H, Abe T, Hashimoto H, Uchida S, Irimajiri S, Hara M, 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;31:243–51.
Kawai S, Hashimoto H, Kondo H, Murayama T, Kiuchi T, Abe T. Comparison of tacrolimus and mizoribine in a randomized, double-blind controlled study in patients with rheumatoid arthritis. J Rheumatol. 2006;33:2153–61.
Furst DE, Saag K, Fleischmann MR, Sherrer Y, Block JA, Schnitzer T, 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;46:2020–8.
Yocum DE, Furst DE, Kaine JL, Baldassare AR, Stevenson JT, Borton MA, et al. Efficacy and safety of tacrolimus in patients with rheumatoid arthritis: a double-blind trial. Arthritis Rheum. 2003;48:3328–37.
Kremer JM, Habros JS, Kolba KS, Kaine JL, Borton MA, Mengle-Gaw LJ, et al. Tacrolimus in rheumatoid arthritis patients receiving concomitant methotrexate: a six-month, open-label study. Arthritis Rheum. 2003;48:2763–8.
Arnett F, Edworthy S, Bloch D, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31:315–24.
DAS-score NL. Home of the DAS. http://www.das-score.nl/www.das-score.nl/. Accessed 27 March 2008.
Matsui T, Kuga Y, Kaneko A, Nishino J, Eto Y, Chiba N, et al. Disease Activity Score 28 (DAS28) using CRP underestimates the disease activity and overestimates the EULAR response criteria compared with DAS28 using ESR in a large observational cohort of rheumatoid arthritis patients in Japan. Ann Rheum Dis. 2007;66:1221–6.
Inoue E, Yamanaka H, Hara M, Tomatsu T, Kamatani N. Comparison of Disease Activity Score (DAS)28-erythrocyte sedimentation rate and DAS28-C-reactive protein threshold values. Ann Rheum Dis. 2007;66:407–9.
Yamanaka H, Tanaka Y, Sekiguchi N, Inoue E, Saito K, Kameda H, et al. Retrospective clinical study on the notable efficacy and related factors of infliximab therapy in a rheumatoid arthritis management group in Japan (RECONFIRM). Mod Rheumatol. 2007;17:28–32.
Miyasaka N, Takeuchi T, Eguchi K. Guidelines for the proper use of etanercept in Japan. Mod Rheumatol. 2006;16:63–7.
Miyasaka N, Takeuchi T, Eguchi K. Proposed Japanese guidelines for the use of infliximab for rheumatoid arthritis. Mod Rheumatol. 2005;15:4–8.
Kawai S, Yamamoto K. Safety of tacrolimus, an immunosuppressive agent, in the treatment of rheumatoid arthritis in elderly patients. Rheumatology. 2006;45:441–4.
Azuma T, Oishi M, Takei M, Sawada S. Tacrolimus-related nocturnal myoclonus of the lower limbs in elderly patients with rheumatoid arthritis. Mod Rheumatol. 2007;17:247–50.
Tsujimura S, Saito K, Nawata M, Nakayamada S, Tanaka Y. Overcoming drug resistance induced by P-glycoprotein on lymphocytes in patients with refractory rheumatoid arthritis. Ann Rheum Dis. 2008;67:380–8.
Saeki T, Ueda K, Tanigawara Y, Hori R, Komano T. Human P-glycoprotein transports cyclosporin A and FK506. J Biol Chem. 1993;268:6077–80.
Acknowledgments
We thank Dr. Takashi Hayashi (Sayo Central Hospital) for providing the data. The authors have no conflicts of interest to disclose.
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An erratum to this article can be found at http://dx.doi.org/10.1007/s10165-008-0148-7
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Morita, Y., Sasae, Y., Sakuta, T. et al. Efficacy of low-dose tacrolimus added to methotrexate in patients with rheumatoid arthritis in Japan: a retrospective study. Mod Rheumatol 18, 379–384 (2008). https://doi.org/10.1007/s10165-008-0071-y
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DOI: https://doi.org/10.1007/s10165-008-0071-y