Tacrolimus for the treatment of fistulas in patients with Crohn's disease: A randomized, placebo-controlled trial

William J. Sandborn; Daniel H. Present; Kim L. Isaacs; Douglas C. Wolf; Eugene Greenberg; Stephen B. Hanauer; Brian G. Feagan; Lloyd Mayer; Therese Johnson; Joseph Galanko; Christopher Martin; Robert S. Sandler

doi:10.1016/S0016-5085(03)00877-1

Tacrolimus for the treatment of fistulas in patients with Crohn's disease: A randomized, placebo-controlled trial

William J. Sandborn^*, Daniel H. Present, Kim L. Isaacs, Douglas C. Wolf, Eugene Greenberg, Stephen B. Hanauer, Brian G. Feagan, Lloyd Mayer, Therese Johnson, Joseph Galanko, Christopher Martin, Robert S. Sandler

^*Corresponding author for this work

Medicine, Gastroenterology Division

Research output: Contribution to journal › Article › peer-review

302 Scopus citations

Abstract

Background & Aims: 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.

Original language	English (US)
Pages (from-to)	380-388
Number of pages	9
Journal	Gastroenterology
Volume	125
Issue number	2
DOIs	https://doi.org/10.1016/S0016-5085(03)00877-1
State	Published - Aug 1 2003

Funding

The principal investigator (W.J.S.) and the other coinvestigators designed the study, recruited the patients, managed the data, performed the statistical analysis, and wrote the manuscript detailing the results of the study. Specifically, the completed case report forms for each patient were sent by investigators to the principal investigator (W.J.S., T.J.) and then to the data management center of the CCFA Clinical Alliance, where the statistical analysis was performed ( J.G., C.M., R.S.S.). The study was funded by research grants from the CCFA and Fujisawa USA. Representatives from Fujisawa USA had the opportunity to review and comment on the study design and on the manuscript, but the principal investigator made the final decisions regarding the design of the study and the content of the manuscript. Supported by research grants from the Crohn’s and Colitis Foundation of America (New York, NY), Fujisawa USA (Deerfield, IL), and the General Clinical Research Centers program of the Division of Research Resources, National Institutes of Health (grant no. RR00046).,

ASJC Scopus subject areas

Gastroenterology
Hepatology

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Sandborn, W. J., Present, D. H., Isaacs, K. L., Wolf, D. C., Greenberg, E., Hanauer, S. B., Feagan, B. G., Mayer, L., Johnson, T., Galanko, J., Martin, C., & Sandler, R. S. (2003). Tacrolimus for the treatment of fistulas in patients with Crohn's disease: A randomized, placebo-controlled trial. Gastroenterology, 125(2), 380-388. https://doi.org/10.1016/S0016-5085(03)00877-1

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title = "Tacrolimus for the treatment of fistulas in patients with Crohn's disease: A randomized, placebo-controlled trial",

abstract = "Background & Aims: 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.",

author = "Sandborn, {William J.} and Present, {Daniel H.} and Isaacs, {Kim L.} and Wolf, {Douglas C.} and Eugene Greenberg and Hanauer, {Stephen B.} and Feagan, {Brian G.} and Lloyd Mayer and Therese Johnson and Joseph Galanko and Christopher Martin and Sandler, {Robert S.}",

note = "Funding Information: The principal investigator (W.J.S.) and the other coinvestigators designed the study, recruited the patients, managed the data, performed the statistical analysis, and wrote the manuscript detailing the results of the study. Specifically, the completed case report forms for each patient were sent by investigators to the principal investigator (W.J.S., T.J.) and then to the data management center of the CCFA Clinical Alliance, where the statistical analysis was performed ( J.G., C.M., R.S.S.). The study was funded by research grants from the CCFA and Fujisawa USA. Representatives from Fujisawa USA had the opportunity to review and comment on the study design and on the manuscript, but the principal investigator made the final decisions regarding the design of the study and the content of the manuscript. Funding Information: Supported by research grants from the Crohn{\textquoteright}s and Colitis Foundation of America (New York, NY), Fujisawa USA (Deerfield, IL), and the General Clinical Research Centers program of the Division of Research Resources, National Institutes of Health (grant no. RR00046)., ",

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TY - JOUR

T1 - Tacrolimus for the treatment of fistulas in patients with Crohn's disease

T2 - A randomized, placebo-controlled trial

AU - Sandborn, William J.

AU - Present, Daniel H.

AU - Isaacs, Kim L.

AU - Wolf, Douglas C.

AU - Greenberg, Eugene

AU - Hanauer, Stephen B.

AU - Feagan, Brian G.

AU - Mayer, Lloyd

AU - Johnson, Therese

AU - Galanko, Joseph

AU - Martin, Christopher

AU - Sandler, Robert S.

N1 - Funding Information: The principal investigator (W.J.S.) and the other coinvestigators designed the study, recruited the patients, managed the data, performed the statistical analysis, and wrote the manuscript detailing the results of the study. Specifically, the completed case report forms for each patient were sent by investigators to the principal investigator (W.J.S., T.J.) and then to the data management center of the CCFA Clinical Alliance, where the statistical analysis was performed ( J.G., C.M., R.S.S.). The study was funded by research grants from the CCFA and Fujisawa USA. Representatives from Fujisawa USA had the opportunity to review and comment on the study design and on the manuscript, but the principal investigator made the final decisions regarding the design of the study and the content of the manuscript. Funding Information: Supported by research grants from the Crohn’s and Colitis Foundation of America (New York, NY), Fujisawa USA (Deerfield, IL), and the General Clinical Research Centers program of the Division of Research Resources, National Institutes of Health (grant no. RR00046).,

PY - 2003/8/1

Y1 - 2003/8/1

N2 - Background & Aims: 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.

AB - Background & Aims: 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.

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Tacrolimus for the treatment of fistulas in patients with Crohn's disease: A randomized, placebo-controlled trial

Abstract

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