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P207. Oral tacrolimus therapy is useful for patients with intractable ulcerative colitis: A result of post-marketing analysis

N. Inoue, R. Ichikawa, J. Miyoshi, K. Natsuoka, T. Hisamatsu, S. Okamoto, H. Ogata, Y. Iwao, T. Hibi

Keio University School of Medicine, Tokyo, Japan

Purpose: Immunosuppressive therapy with intravenous cyclosporine A is an alternative treatment option to total colectomy for patients with severely-active ulcerative colitis (UC), while the benefits of oral administration of tacrolimus are not well defined. As it was recently approved for clinical use in Japan, we evaluate the efficacy and safety of tacrolimus in patients with intractable UC.

Methods: Twenty-eight patients with intractable UC, including those refractory to corticosteroids (n = 13), dependent to corticosteroids (n = 14), were orally administered tacrolimus to induce remission with trough whole-blood levels of 10–15 ng/mL for two week and then maintained with those of 5–10 ng/mL. Median treatment duration was 6 months (3–13 months) and median follow-up duration was 11.5 months (4–15 months). Evaluation of the clinical response was based on a modified Truelove-Witts clinical activity index (CAI) and endoscopic response was assessed by Baron's score and endoscopic activity index (EAI; J Gastroenterol 45: 936, 2010) before and three months after starting the treatment. Moreover, prognosis during or after the treatment with tacrolimus was assessed.

Results: Trough levels of the drug reached to target level in 7.1 days (mean, 2–19 days). CAI scores significantly decreased from 11.4±4.2 to 5.5±3.0 at week 2 (p < 0.0001). Remission was achieved in 43%, improvement was achieved in 39% of patients while 18% of patients did not respond to treatment. Endoscopic activities decreased at three months in 16 of 23 patients examined. Corticosteroids were successfully tapered or discontinued in all of 10 patients treated with corticosteroids at the initiation of tacrolimus therapy. Seven patients underwent colectomy by 12 months. A life-table analysis for all patients revealed that the overall percentages of patients who had not required colectomy was 70.0% at 12 months. There were no lethal adverse reactions to tacrolimus in our series, but the reversible events encountered besides minor tremor were as follows: hypomagnesemia (39.3%); renal dysfunction (3.6%); hyperkalaemia (3.6%); and infections (7.1%; Pneumocystis cariniii pneumonia and Clostridium difficile-associated enteritis); and none of these required discontinuation of tacrolimus.

Conclusion: These findings suggested that short-term oral administration of tacrolimus produced a good clinical response comparable to cyclosporine A in our institute (J Gastroenterol 2010 Jul 8. Epub) as well as steroid tapering effect and endoscopic improvement in patients with intractable UC. Infection was considered to be closely monitored.