title: Double-blind, placebo-controlled trial of oral tacrolimus (FK506) in the management of hospitalized patients with steroid-refractory ulcerative colitis.
abstract: 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.
authors: Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
authors: Haruhiko
authors: H
authors: Ogata
authors: Jun
authors: J
authors: Kato
authors: Fumihito
authors: F
authors: Hirai
authors: Nobuyuki
authors: N
authors: Hida
authors: Toshiyuki
authors: T
authors: Matsui
authors: Takayuki
authors: T
authors: Matsumoto
authors: Katsuyoshi
authors: K
authors: Koyanagi
authors: Toshifumi
authors: T
authors: Hibi
mesh_terms: D000284:Administration, Oral; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D019468:Disease Management; D004311:Double-Blind Method; D004351:Drug Resistance; D005500:Follow-Up Studies; D006760:Hospitalization; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D010349:Patient Compliance; D012074:Remission Induction; D013256:Steroids / Q000494:pharmacology*; D016559:Tacrolimus / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D013256:Steroids; D016559:Tacrolimus