Abstract
Background
Recent evidence indicates that intravenous or oral therapy with tacrolimus (FK-506) is effective in treating patients with Crohn’s disease. We evaluated the usefulness of tacrolimus therapy for Japanese patients with refractory Crohn’s disease.
Methods
Fourteen adult Japanese patients with Crohn’s disease that was refractory to conventional therapies, including prednisolone (n = 5), azathioprine (n = 6), and infliximab (n = 5), were enrolled. Treatment with tacrolimus was started orally or intravenously and aimed for serum trough levels of 10–15 ng/ml. After the patients achieved clinical improvement, tacrolimus maintenance therapy was administered to maintain the trough level at 5–10 ng/ml.
Results
All patients achieved remission or significant improvement 40 days after starting tacrolimus treatment. By 120 days after the start of therapy, 9 (64%) patients achieved remission, 2 patients (14%) achieved significant improvement, and only 3 patients (21%) relapsed. The relapsed patients were treated with infliximab therapy and achieved remission. Steroids were discontinued by the 5 patients who had taken steroids before the study began. Adverse effects of tacrolimus included a temporary increase in serum creatinine concentration (n = 1, 7%), hyperkalemia (n = 1, 7%), and tremor (n = 1, 7%).
Conclusions
Tacrolimus therapy is effective and well tolerated in patients with Crohn’s disease that is refractory to conventional therapies.
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References
Kino T, Inamura N, Sakai F, Nakahara K, Goto T, Okuhara M, et al. Effect of FK-506 on human mixed lymphocyte reaction in vitro. Transplant Proc 1987;19:36–39.
Kino T, Hatanaka H, Miyata S, Inamura N, Nishiyama M, Yajima T, et al. FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro. J Antibiot (Tokyo) 1987;40:1256–1265.
Goto T, Kino T, Hatanaka H, Nishiyama M, Okuhara M, Kohsaka M, et al. Discovery of FK-506, a novel immunosuppressant isolated from Streptomyces tsukubaensis. Transplant Proc 1987;19:4–8.
Busuttil RW, Lake JR. Role of tacrolimus in the evolution of liver transplantation. Transplantation 2004;77:S44–S51.
Vincenti F. A decade of progress in kidney transplantation. Transplantation 2004;77:S52–S61.
Goulet O, Michel JL, Jobert A, Damotte D, Colomb V, Cezard JP, et al. Small bowel transplantation alone or with the liver in children: changes by using FK506. Transplant Proc 1998;30:1569–1570.
Zabawski EJ, Costner M, Cohen JB, Cockerell CJ. Tacrolimus: pharmacology and therapeutic uses in dermatology. Int J Dermatol 2000;39:721–727.
Ierardi E, Principi M, Francavilla R, Pisani A, Rendina M, Ingrosso M, et al. Oral tacrolimus long-term therapy in patients with Crohn’s disease and steroid resistance. Aliment Pharmacol Ther 2001;15:371–377.
Hogenauer C, Wenzl HH, Hinterleitner TA, Petritsch W. Effect of oral tacrolimus (FK 506) on steroid-refractory moderate/severe ulcerative colitis. Aliment Pharmacol Ther 2003;18:415–423.
Sandborn WJ, Present DH, Isaacs KL, Wolf DC, Greenberg E, Hanauer SB, et al. Tacrolimus for the treatment of fistulas in patients with Crohn’s disease: a randomized, placebo-controlled trial. Gastroenterology 2003;125:380–388.
Gonzalez-Lama Y, Abreu L, Vera MI, Pastrana M, Tabernero S, Revilla J, et al. Long-term oral tacrolimus therapy in refractory to infliximab fistulizing Crohn’s disease: a pilot study. Inflamm Bowel Dis 2005;11:8–15.
Harvey RF, Bradshaw JM. A simple index of Crohn’s-disease activity. Lancet 1980;1:514.
Befeler AS, Lissoos TW, Schiano TD, Conjeevaram H, Dasgupta KA, Millis JM, et al. Clinical course and management of inflammatory bowel disease after liver transplantation. Transplantation 1998;65:393–396.
Fellermann K, Ludwig D, Stahl M, David-Walek T, Stange EF. Steroid-unresponsive acute attacks of inflammatory bowel disease: immunomodulation by tacrolimus (FK506). Am J Gastroenterol 1998;93:1860–1866.
Egan LJ, Sandborn WJ, Tremaine WJ. Clinical outcome following treatment of refractory inflammatory and fistulizing Crohn’s disease with intravenous cyclosporine. Am J Gastroenterol 1998;93:442–448.
Matsuhashi N, Nakajima A, Watanabe K, Komeno Y, Suzuki A, Ohnishi S, et al. Tacrolimus in corticosteroid-resistant ulcerative colitis. J Gastroenterol 2000;35:635–640.
Ogata H, Matsui T, Nakamura M, Iida M, Takazoe M, Suzuki Y, Hibi T. A randomised dose finding study of oral tacrolimus (FK506) therapy in refractory ulcerative colitis. Gut 2006;55:1255–1262.
Hanke JH, Nichols LN, Coon ME. FK506 and rapamycin selectively enhance degradation of IL-2 and GM-CSF mRNA. Lymphokine Cytokine Res 1992;11:221–231.
Wang SC, Jordan ML, Tweardy DJ, Wright J, Hoffman RA, Simmons RL. FK-506 inhibits proliferation and IL-4 messenger RNA production by a T-helper 2 cell line. J Surg Res 1992;53:199–202.
Tocci MJ, Matkovich DA, Collier KA, Kwok P, Dumont F, Lin S, et al. The immunosuppressant FK506 selectively inhibits expression of early T cell activation genes. J Immunol 1989;143:718–726.
Gummert JF, Ikonen T, Morris RE. Newer immunosuppressive drugs: a review. J Am Soc Nephrol 1999;10:1366–1380.
Sandborn WJ. A review of immune modifier therapy for inflammatory bowel disease: azathioprine, 6-mercaptopurine, cyclosporine, and methotrexate. Am J Gastroenterol 1996;91:423–433.
Jain A, Venkataramanan R, Lever J, Warty V, Abu-Elmagd K, Furukawa H, et al. FK 506 in small bowel transplant recipients: pharmacokinetics and dosing. Transplant Proc 1994;26:1609–1610.
Winkler M, Ringe B, Baumann J, Loss M, Wonigeit K, Pichlmayr R. Plasma vs. whole blood for therapeutic drug monitoring of patients receiving FK 506 for immunosuppression. Clin Chem 1994;40:2247–2253.
Laskow DA, Vincenti F, Neylan JF, Mendez R, Matas AJ. An open-label, concentration-ranging trial of FK506 in primary kidney transplantation: a report of the United States Multicenter FK506 Kidney Transplant Group. Transplantation 1996;62:900–905.
Kershner RP, Fitzsimmons WE. Relationship of FK506 whole blood concentrations and efficacy and toxicity after liver and kidney transplantation. Transplantation 1996;62:920–926.
Masuda S, Uemoto S, Hashida T, Inomata Y, Tanaka K, Inui K. Effect of intestinal P-glycoprotein on daily tacrolimus trough level in a living-donor small bowel recipient. Clin Pharmacol Ther 2000;68:98–103.
Masuda S, Uemoto S, Goto M, Fujimoto Y, Tanaka K, Inui K. Tacrolimus therapy according to mucosal MDR1 levels in smallbowel transplant recipients. Clin Pharmacol Ther 2004;75:352–361.
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Tamaki, H., Nakase, H., Matsuura, M. et al. The effect of tacrolimus (FK-506) on Japanese patients with refractory Crohn’s disease. J Gastroenterol 43, 774–779 (2008). https://doi.org/10.1007/s00535-008-2229-y
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DOI: https://doi.org/10.1007/s00535-008-2229-y