Double-blind, placebo-controlled trial of oral tacrolimus (FK506) in the management of hospitalized patients with steroid-refractory ulcerative colitis.
Author(s): Ogata H, Kato J, Hirai F, Hida N, Matsui T, Matsumoto T, Koyanagi K, Hibi T
Affiliation(s): Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Publication date & source: 2011-09-01, Inflamm Bowel Dis., [Epub ahead of print]
BACKGROUND: We report a multicenter study of oral tacrolimus (FK506) therapy in steroid-refractory ulcerative colitis (UC). METHODS: In a placebo-controlled, double-blind study, 62 patients with steroid-refractory, moderate-to-severe UC were randomized into either a tacrolimus group or a placebo for 2 weeks. Patients were evaluated using the Disease Activity Index (DAI). As an entry criterion, patients had to have a total DAI score of 6 or more as well as a mucosal appearance subscore of 2 or 3. Clinical response was defined as improvement in all DAI subscores. Mucosal healing was defined as mucosal appearance subscore of 0 or 1. Clinical remission was defined as a total DAI score </=2 with an individual subscore of 0 or 1. RESULTS: The mean total DAI score at study entry was 9.8 +/- 1.61 in the tacrolimus group and 9.1 +/- 1.05 in the placebo group. At week 2 the clinical response rate was 50.0% (16/32) in the tacrolimus group and 13.3% (4/30) in the placebo group (P = 0.003). The rate of mucosal healing observed was 43.8% (14/32) in the tacrolimus group and 13.3% (4/30) in the placebo group (P = 0.012) and the rate of clinical remission observed was 9.4% (3/32) in the tacrolimus group and 0.0% (0/30) in the placebo group (P = 0.238). The therapies in this study were well tolerated, with only minor side effects. CONCLUSIONS: Oral tacrolimus therapy in patients with steroid-refractory UC shortened the acute phase and induced rapid mucosal healing. These results suggest that tacrolimus therapy is useful as an alternative therapy for steroid-refractory UC. (Inflamm Bowel Dis 2011;). Copyright (c) 2011 Crohn's & Colitis Foundation of America, Inc.