title: Tacrolimus for the treatment of fistulas in patients with Crohn's disease: a randomized, placebo-controlled trial.
abstract: OBJECTIVE
  This study determined the effectiveness of tacrolimus for the treatment of Crohn's disease fistulas.
  
  
  METHODS
  The study was a randomized, double-blind, placebo-controlled, multicenter clinical trial. Forty-eight patients with Crohn's disease and draining perianal or enterocutaneous fistulas were randomized to treatment with oral tacrolimus 0.2 mg. kg(-1). day(-1) or placebo for 10 weeks. The primary outcome measure was fistula improvement as defined by closure of >/=50% of particular fistulas that were draining at baseline and maintenance of that closure for at least 4 weeks. A secondary outcome measure was fistula remission as defined by closure of all fistulas and maintenance of that closure for at least 4 weeks.
  
  
  RESULTS
  Forty-three percent of tacrolimus-treated patients had fistula improvement compared with 8% of placebo-treated patients (P = 0.004). Ten percent of tacrolimus-treated patients had fistula remission compared with 8% of placebo-treated patients (P = 0.86). Adverse events significantly associated with tacrolimus, including headache, increased serum creatinine level, insomnia, leg cramps, paresthesias, and tremor, were managed with dose reduction.
  
  
  CONCLUSIONS
  Oral tacrolimus 0.2 mg. kg(-1). day(-1) is effective for fistula improvement, but not fistula remission, in patients with perianal Crohn's disease. Adverse events associated with tacrolimus can be managed by dose reduction. Lower doses of tacrolimus should be evaluated.
authors.affiliation: Mayo Clinic, 200 First Street Southwest, Rochester, Minnesota 55905, USA. sandborn.william@mayo.edu
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Present
authors.forename: Kim L
authors.initials: KL
authors.lastname: Isaacs
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Wolf
authors.forename: Eugene
authors.initials: E
authors.lastname: Greenberg
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Hanauer
authors.forename: Brian G
authors.initials: BG
authors.lastname: Feagan
authors.forename: Lloyd
authors.initials: L
authors.lastname: Mayer
authors.forename: Therese
authors.initials: T
authors.lastname: Johnson
authors.forename: Joseph
authors.initials: J
authors.lastname: Galanko
authors.forename: Christopher
authors.initials: C
authors.lastname: Martin
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sandler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003424:Crohn Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007412:Intestinal Fistula / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus