Rheumatology International

, Volume 31, Issue 6, pp 757–763 | Cite as

Single center prospective study of tacrolimus efficacy and safety in the treatment of various manifestations in systemic lupus erythematosus

  • Katsuya Suzuki
  • Hideto Kameda
  • Koichi Amano
  • Hayato Nagasawa
  • Hirofumi Takei
  • Eiko Nishi
  • Ayumi Okuyama
  • Kensei Tsuzaka
  • Tsutomu Takeuchi
Original Article

Abstract

The aim of this study was to prospectively evaluate the efficacy and safety of tacrolimus (TAC) in various manifestations of systemic lupus erythematosus (SLE) patients in daily clinical practice. Each of the 21 TAC-treated patients with SLE in our care over 2 years was enrolled in this open-label trial. Patients were administered TAC at a dosage of 1–6 mg once daily, followed up for 24 weeks. Efficacy and safety were evaluated utilizing clinical and laboratory findings. As treatment targets, TAC was preferentially used with oral corticosteroid administration for mild active manifestations such as arthritis, skin eruptions, or asymptomatic nephritis. In efficacy, the mean value of the SLE disease activity index was significantly reduced to 4.1, 2.7, 1.8, and 1.2 (N = 21, 20, 16 and 13) at 0, 4, 12, and 24 weeks, respectively. In eight cases, treatment was discontinued within 24 weeks due to insufficient effects (6 cases) and side effects (2 cases). Non-serious side effects were observed in only five cases (23.8%) over 24 weeks. TAC can be considered both effective and safe for the treatment of various manifestations of SLE.

Keywords

Tacrolimus Systemic lupus erythematosus T cell 

Notes

Conflict of interest statement

None.

References

  1. 1.
    D’Cruz DP, Khamashta MA, Hughes GR (2007) Systemic lupus erythematosus. Lancet 369:587–596PubMedCrossRefGoogle Scholar
  2. 2.
    Rahman A, Isenberg DA (2008) Systemic lupus erythematosus. N Engl J Med 358:929–939PubMedCrossRefGoogle Scholar
  3. 3.
    Takeuchi T, Tsuzaka K, Abe T et al (2005) T cell abnormalities in systemic lupus erythematosus. Autoimmunity 38:339–346PubMedCrossRefGoogle Scholar
  4. 4.
    Bertsias G, Ioannidis JP, Boletis J et al (2008) Task force of the EULAR standing committee for international clinical studies including therapeutics. EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. Ann Rheum Dis 67:195–205PubMedCrossRefGoogle Scholar
  5. 5.
    Siekierka JJ, Sigal NH (1992) FK-506 and cyclosporin A: immunosuppressive mechanism of action and beyond. Curr Opin Immunol 4:548–552PubMedCrossRefGoogle Scholar
  6. 6.
    Sakuma S, Kato Y, Nishigaki F et al (2000) FK506 potently inhibits T cell activation induced TNF-alpha and IL-1beta production in vitro by human peripheral blood mononuclear cells. Br J Pharmacol 130:1655–1663PubMedCrossRefGoogle Scholar
  7. 7.
    Sakuma S, Kato Y, Nishigaki F et al (2001) Effects of FK506 and other immunosuppressive anti-rheumatic agents on T cell activation mediated IL-6 and IgM production in vitro. Int Immunopharmacol 1:749–757PubMedCrossRefGoogle Scholar
  8. 8.
    European FK506 Multicentre Liver Study Group (1994) Randomised trial comparing tacrolimus (FK506) and cyclosporin in prevention of liver allograft rejection. Lancet 344:423–428CrossRefGoogle Scholar
  9. 9.
    The U.S. Multicenter FK506 Liver Study Group (1994) A comparison of tacrolimus (FK 506) and cyclosporine for immunosuppression in liver transplantation. N Engl J Med 331:1110–1115CrossRefGoogle Scholar
  10. 10.
    Schleibner S, Krauss M, Wagner K et al (1995) FK 506 versus cyclosporin in the prevention of renal allograft rejection—European pilot study: six-week results. Transpl Int 8:86–90PubMedGoogle Scholar
  11. 11.
    Laskow DA, Vincenti F, Neylan JF, Mendez R, Matas AJ (1996) An open-label, concentration-ranging trial of FK506 in primary kidney transplantation: a report of the United States Multicenter FK506 Kidney Transplant Group. Transplantation 62:900–905PubMedCrossRefGoogle Scholar
  12. 12.
    Konishi T, Yoshiyama Y, Takamori M, Yagi K, Mukai E, Saida T (2003) Japanese FK506 MG Study Group. Clinical study of FK506 in patients with myasthenia gravis. Muscle Nerve 28:570–574PubMedCrossRefGoogle Scholar
  13. 13.
    Gremillion RB, Posever JO, Manek N, West JP, van Volen-Hoven RF (1999) Tacrolimus (FK506) in the treatment of severe, refractory rheumatoid arthritis: initial experience in 12 patients. J Rheumatol 26:2332–2336PubMedGoogle Scholar
  14. 14.
    Furst DE, Saag K, Fleischmann MR, Sherrer Y, Block JA, Schnitzer T et al (2002) 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 46:2020–2028PubMedCrossRefGoogle Scholar
  15. 15.
    Kondo H, Abe T, Hashimoto H et al (2004) Efficacy and safety of tacrolimus (FK506) in treatment of rheumatoid arthritis: a randomized, double blind, placebo controlled dose-finding study. J Rheumatol 31:243–251PubMedGoogle Scholar
  16. 16.
    Suzuki K, Kameda H, Amano K et al (2009) Single center prospective study of tacrolimus efficacy and safety in treatment of rheumatoid arthritis. Rheumatol Int 29:431–436PubMedCrossRefGoogle Scholar
  17. 17.
    Hochberg MC (1997) Diagnostic and Therapeutic Criteria Committee of the American College of Rheumatology. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40(9):1725PubMedCrossRefGoogle Scholar
  18. 18.
    Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 35:630–640PubMedCrossRefGoogle Scholar
  19. 19.
    Duddridge M, Powell RJ (1997) Treatment of severe and difficult cases of systemic lupus erythematosus with tacrolimus. A report of three cases. Ann Rheum Dis 56(11):690–692PubMedCrossRefGoogle Scholar
  20. 20.
    Yoon KH (2004) Successful usage of tacrolimus (FK506) in resistant/relapsed rheumatic diseases. APLAR J Rheumatol 7:44–48CrossRefGoogle Scholar
  21. 21.
    Politt D, Heintz B, Floege J, Mertens PR (2004) Tacrolimus- (FK506) based immunosuppression in severe systemic lupus erythematosus. Clin Nephrol 62:49–53PubMedGoogle Scholar
  22. 22.
    Mok CC, Tong KH, To CH, Siu YP, Au TC (2005) Tacrolimus for induction therapy of diffuse proliferative lupus nephritis: an open-labeled pilot study. Kidney Int 68:813–817PubMedCrossRefGoogle Scholar
  23. 23.
    Mok CC (2006) Therapeutic options for resistant lupus nephritis. Semin Arthritis Rheum 36:71–81PubMedCrossRefGoogle Scholar
  24. 24.
    Tse KC, Lam MF, Tang SC, Tang CS, Chan TM (2007) A pilot study on tacrolimus treatment in membranous or quiescent lupus nephritis with proteinuria resistant to angiotensin inhibition or blockade. Lupus 16:46–51PubMedCrossRefGoogle Scholar
  25. 25.
    Oki E, Tsugawa K, Suzuki K, Tanaka H (2007) Effective treatment of a refractory case of systemic lupus erythematosus with low-dose tacrolimus. Nippon Jinzo Gakkai Shi 49:1020–1024PubMedGoogle Scholar
  26. 26.
    Bao H, Liu ZH, Xie HL, Hu WX, Zhang HT, Li LS (2008) Successful treatment of class V + IV lupus nephritis with multitarget therapy. J Am Soc Nephrol 19:2001–2010PubMedCrossRefGoogle Scholar
  27. 27.
    Szeto CC, Kwan BC, Lai FM et al (2008) Tacrolimus for the treatment of systemic lupus erythematosus with pure class V nephritis. Rheumatology (Oxford) 47:1678–1681CrossRefGoogle Scholar
  28. 28.
    Dong G, Panaro F, Bogetti D et al (2005) Standard chronic immunosuppression after kidney transplantation for systemic lupus erythematosus eliminates recurrence of disease. Clin Transplant 19:56–60PubMedCrossRefGoogle Scholar
  29. 29.
    Tang H, Chelamcharla M, Baird BC, Shihab FS, Koford JK, Goldfarb-Rumyantzev AS (2008) Factors affecting kidney-transplant outcome in recipients with lupus nephritis. Clin Transplant 22:263–272PubMedCrossRefGoogle Scholar
  30. 30.
    Tanaka H, Oki E, Tsugawa K, Nonaka K, Suzuki K, Ito E (2007) Effective treatment of young patients with pediatric-onset, long-standing lupus nephritis with tacrolimus given as a single daily dose: an open-label pilot study. Lupus 16:896–900PubMedCrossRefGoogle Scholar
  31. 31.
    Maruoka H, Honda S, Takeo M, Koga T, Fukuda T, Aizawa H (2006) Tacrolimus treatment for refractory lupus cystitis. Mod Rheumatol 16:264–266PubMedCrossRefGoogle Scholar
  32. 32.
    Mok CC, To CH, Mak A, Poon WL (2008) Immunoablative cyclophosphamide for refractory lupus-related neuromyelitis optica. J Rheumatol 35:172–174PubMedGoogle Scholar
  33. 33.
    Yoshimasu T, Ohtani T, Sakamoto T, Oshima A, Furukawa F (2002) Topical FK506 (tacrolimus) therapy for facial erythematous lesions of cutaneous lupus erythematosus, dermatomyositis. Eur J Dermatol 12:50–52PubMedGoogle Scholar
  34. 34.
    Walker SL, Kirby B, Chalmers RJ (2002) The effect of topical tacrolimus on severe recalcitrant chronic discoid lupus erythematosus. Br J Dermatol 147:405–406PubMedCrossRefGoogle Scholar
  35. 35.
    Kanekura T, Yoshii N, Terasaki K, Miyoshi H, Kanzaki T (2003) Efficacy of topical tacrolimus for treating the malar rash of systemic lupus erythematosus. Br J Dermatol 148:353–356PubMedCrossRefGoogle Scholar
  36. 36.
    Lampropoulos CE, Sangle S, Harrison P, Hughes GR, D’Cruz DP (2004) Topical tacrolimus therapy of resistant cutaneous lesions in lupus erythematosus: a possible alternative. Rheumatology (Oxford) 43:1383–1385CrossRefGoogle Scholar
  37. 37.
    Morton SJ, Powell RJ (2000) Cyclosporin and tacrolimus: their use in a routine clinical setting for scleroderma. Rheumatology (Oxford) 39:865–869CrossRefGoogle Scholar
  38. 38.
    Oddis CV, Sciurba FC, Elmagd KA, Starzl TE (1999) Tacrolimus in refractory polymyositis with interstitial lung disease. Lancet 353:1762–1763PubMedCrossRefGoogle Scholar
  39. 39.
    Ochi S, Nanki T, Takada K et al (2005) Favorable outcomes with tacrolimus in two patients with refractory interstitial lung disease associated with polymyositis/dermatomyositis. Clin Exp Rheumatol 23:707–710PubMedGoogle Scholar
  40. 40.
    Nalda AM, Caballero CM, Guimeral CA, Rom MB, García PB (2006) Efficacy of tacrolimus (FK-506) in the treatment of recalcitrant juvenile dermatomyositis: study of 6 cases. Med Clin (Barc) 127:697–701CrossRefGoogle Scholar
  41. 41.
    Kitahara K, Kawai S (2007) Cyclosporine and tacrolimus for the treatment of rheumatoid arthritis. Curr Opin Rhumatol 19(3):238–245CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Katsuya Suzuki
    • 1
  • Hideto Kameda
    • 1
  • Koichi Amano
    • 1
  • Hayato Nagasawa
    • 1
  • Hirofumi Takei
    • 1
  • Eiko Nishi
    • 1
  • Ayumi Okuyama
    • 1
  • Kensei Tsuzaka
    • 1
  • Tsutomu Takeuchi
    • 1
    • 2
  1. 1.Division of Rheumatology/Clinical Immunology, Department of Medicine, Saitama Medical CenterSaitama Medical UniversityKawagoeJapan
  2. 2.Division of Rheumatology/Clinical Immunology, Department of Internal MedicineKeio UniversityTokyoJapan

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