Long-term effect of tacrolimus therapy in patients with refractory ulcerative colitis S. YAMAMOTO*, H. NAKASE*, S. MIKAMI*, S. INOUE*, T. YOSHINO*, Y. TAKEDA*, K. KASAHARA*, S. UENO*, N. UZA*, H. KITAMURA*, H. TAMAKI*, M. MATSUURA*, K. INUI  & T. CHIBA* *Department of Gastroenterology and Hepatology, Graduate School of Medi- cine and  Department of Pharmacy, Graduate School of Medicine and Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan Correspondence to: Dr H. Nakase, Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. E-mail: hiropy_n@kuhp.kyoto-u.ac.jp Publication data Submitted 15 May 2008 Accepted 8 June 2008 Epub Accepted Article 11 June 2008 SUMMARY Background Little is known about long-term outcome of tacrolimus therapy for ulcerative colitis. Aim To evaluate long-term efficacy and safety of tacrolimus in Japanese patients with refractory ulcerative colitis. Methods Twenty-seven patients with UC refractory to conventional therapy were administered tacrolimus with trough whole-blood levels of 10– 15 ng / mL to induce remission and 5–10 ng / mL to maintain remission. Median treatment duration was 11 months (1–39 months) and median follow-up duration was 17 months (2–65 months). Evaluation of the clinical response was based on a modified Truelove–Witts severity index (MTWSI). Results Tacrolimus produced a clinical response in 21 patients (77.8%), and remission was achieved in 19 of these 21 (70.4%) within 30 days. Over- all cumulative colectomy-free survival was estimated as 62.3% at 65 months. In 18 of 19 patients treated with corticosteroids at the initi- ation of tacrolimus therapy, corticosteroids were discontinued or tapered. Adverse events were tremor (25.9%), renal function impairment (18.5%), infectious disease (14.8%), hot flashes (11.1%), hyperkalaemia (7.4%), headache (7.4%), epigastralgia (7.4%) and nausea (3.7%). No mortality occurred. Conclusion Long-term administration of tacrolimus appears to be an effective and well-tolerated treatment for Japanese patients with refractory ulcerative colitis. Aliment Pharmacol Ther 28, 589–597 Alimentary Pharmacology & Therapeutics ª 2008 The Authors 589 Journal compilation ª 2008 Blackwell Publishing Ltd doi:10.1111/j.1365-2036.2008.03764.x