Double-blind, placebo-controlled trial of oral tacrolimus (FK506) in the management of hospitalized patients with steroid-refractory ulcerative colitis

Inflamm Bowel Dis. 2012 May;18(5):803-8. doi: 10.1002/ibd.21853. Epub 2011 Sep 1.


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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Colitis, Ulcerative / drug therapy*
  • Disease Management
  • Double-Blind Method
  • Drug Resistance*
  • Follow-Up Studies
  • Hospitalization
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Patient Compliance
  • Remission Induction
  • Steroids / pharmacology*
  • Tacrolimus / therapeutic use*
  • Treatment Outcome


  • Immunosuppressive Agents
  • Steroids
  • Tacrolimus