Tacrolimus for the treatment of fistulas in patients with Crohn's disease: a randomized, placebo-controlled trial.
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.
Sandborn
William J
WJ
Mayo Clinic, 200 First Street Southwest, Rochester, Minnesota 55905, USA. sandborn.william@mayo.edu
Present
Daniel H
DH
Isaacs
Kim L
KL
Wolf
Douglas C
DC
Greenberg
Eugene
E
Hanauer
Stephen B
SB
Feagan
Brian G
BG
Mayer
Lloyd
L
Johnson
Therese
T
Galanko
Joseph
J
Martin
Christopher
C
Sandler
Robert S
RS
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*
D007166:Immunosuppressive Agents; D016559:Tacrolimus