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

Haruhiko Ogata, Jun Kato, Fumihito Hirai, Nobuyuki Hida, Toshiyuki Matsui, Takayuki Matsumoto, Katsuyoshi Koyanagi, Toshifumi Hibi

Research output: Contribution to journalArticle

116 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)803-808
Number of pages6
JournalInflammatory Bowel Diseases
Volume18
Issue number5
DOIs
Publication statusPublished - 2012 May

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Tacrolimus
Ulcerative Colitis
Steroids
Placebos
Therapeutics
Complementary Therapies
Double-Blind Method
Multicenter Studies

Keywords

  • Immunosuppressive therapy
  • Tacrolimus
  • Ulcerative colitis

ASJC Scopus subject areas

  • Gastroenterology
  • Immunology and Allergy

Cite this

Double-blind, placebo-controlled trial of oral tacrolimus (FK506) in the management of hospitalized patients with steroid-refractory ulcerative colitis. / Ogata, Haruhiko; Kato, Jun; Hirai, Fumihito; Hida, Nobuyuki; Matsui, Toshiyuki; Matsumoto, Takayuki; Koyanagi, Katsuyoshi; Hibi, Toshifumi.

In: Inflammatory Bowel Diseases, Vol. 18, No. 5, 05.2012, p. 803-808.

Research output: Contribution to journalArticle

Ogata, Haruhiko ; Kato, Jun ; Hirai, Fumihito ; Hida, Nobuyuki ; Matsui, Toshiyuki ; Matsumoto, Takayuki ; Koyanagi, Katsuyoshi ; Hibi, Toshifumi. / Double-blind, placebo-controlled trial of oral tacrolimus (FK506) in the management of hospitalized patients with steroid-refractory ulcerative colitis. In: Inflammatory Bowel Diseases. 2012 ; Vol. 18, No. 5. pp. 803-808.
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AU - Hida, Nobuyuki

AU - Matsui, Toshiyuki

AU - Matsumoto, Takayuki

AU - Koyanagi, Katsuyoshi

AU - Hibi, Toshifumi

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AB - 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.

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