Digestive Diseases and Sciences

, Volume 64, Issue 10, pp 2945–2954 | Cite as

Therapeutic Efficacy and Adverse Events of Tacrolimus in Patients with Crohn’s Disease: Systematic Review and Meta-Analysis

  • Tomoya Iida
  • Masanori Nojima
  • Hiroshi NakaseEmail author
Original Article



Only a few randomized controlled trials (RCTs) and some uncontrolled trials have reported the efficacy and adverse events (AEs) of tacrolimus (Tac) in patients with refractory Crohn’s disease (CD). The aim of this study was to undertake a systematic review and meta-analysis of the therapeutic efficacy and AEs of Tac in patients with CD.


We investigated studies reporting the therapeutic efficacy of Tac in patients with CD from 1950 until December 2017. Study subjects were categorized into three groups: systemic administration of Tac for patients with luminal CD (Group 1); systemic administration of Tac for patients with perianal CD (Group 2); and topical administration of Tac for patients with localized CD (Group 3). The primary endpoint of this study was the remission rate. Secondary endpoints were partial response rate, factors related to remission, and the incidence of AEs.


The remission rate of Group 1, 2, and 3 was 37.1, 32.0, and 22.7%, respectively. The partial response rate of those was 42.3, 42.9, and 44.3%, respectively. In addition, the incidence of AEs of those was 50.9, 65.5, and 40.0%, respectively. No life-threatening AEs were observed in any study.


This systematic review and meta-analysis demonstrated that Tac therapy was effective for subpopulation of CD patients and that the incidence of AEs was tolerable. Therefore, Tac therapy should be considered an option for patients with CD. However, there have been few well-designed RCTs on this subject and further studies are required.


Crohn’s disease Tacrolimus Systematic review Meta-analysis 



This work was supported in part by Health and Labour Sciences Research Grants for research on intractable diseases from the Ministry of Health, Labour and Welfare of Japan (Investigation and Research for Intractable Inflammatory Bowel Disease) and the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number JP17J02428 (to T.I.) and JP18H02799 (to H.N.). The funders of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.

Author’s contribution

All authors helped to perform the research. Iida T and Nakase H designed the study. Iida T and Nakase H collected the data, and Nojima M analyzed it. Iida T and Nakase H wrote the manuscript. Nakase H directed the research. All authors have approved the final draft of the manuscript.

Compliance with ethical Ssandards

Conflict of interest

Nakase H has conflict of interest to Tanabe Pharmaceutical Co. Ltd., Mochida Pharmaceutical Co. Ltd., Janssen Pharmaceutical K.K., Hoya Group Pentax Medical, Boehringer Ingelheim GmbH, and Daiichi Sankyo Company, Limited (to HN). All of them had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.

Supplementary material

10620_2019_5619_MOESM1_ESM.docx (53 kb)
Supplementary material 1 (DOCX 52 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Gastroenterology and HepatologySapporo Medical University School of MedicineSapporoJapan
  2. 2.Center for Translational Research, The Institute of Medical Science HospitalThe University of TokyoTokyoJapan

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