Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2019; 25(13): 1603-1617
Published online Apr 7, 2019. doi: 10.3748/wjg.v25.i13.1603
Performance of tacrolimus in hospitalized patients with steroid-refractory acute severe ulcerative colitis
Peter Hoffmann, Cyrill Wehling, Johannes Krisam, Jan Pfeiffenberger, Nina Belling, Annika Gauss
Peter Hoffmann, Cyrill Wehling, Jan Pfeiffenberger, Nina Belling, Annika Gauss, Department of Gastroenterology and Hepatology, Heidelberg University Hospital, Heidelberg 69120, Germany
Johannes Krisam, Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg 69120, Germany
Author contributions: Hoffmann P and Gauss A collected and analyzed the data; Gauss A wrote the manuscript; Wehling C, Pfeiffenberger J, and Belling N helped with data analyses and interpretation; Krisam J assisted with statistical analyses; all authors critically reviewed the manuscript and approved of its contents.
Institutional review board statement: The study was reviewed and approved by the Heidelberg University Institutional Review Board.
Informed consent statement: The requirement for informed consent was waived due to the retrospective nature of the study.
Conflict-of-interest statement: None declared.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Annika Gauss, MD, Assistant Professor, Department of Gastroenterology and Hepatology, Heidelberg University Hospital, Im Neuenheimer Feld 410, Heidelberg 69120, Germany.
Telephone: +49-6221568705 Fax: +49-6221565255
Received: February 14, 2019
Peer-review started: February 14, 2019
First decision: February 21, 2019
Revised: February 23, 2019
Accepted: March 11, 2019
Article in press: March 12, 2019
Published online: April 7, 2019
Research background

Steroid-refractory acute severe ulcerative colitis is a life-threatening medical condition requiring hospitalization and frequently emergency colectomy. Although there is a steadily growing choice of medications for ulcerative colitis, the treatment of steroid-refractory acute severe ulcerative colitis continues to be very challenging. Calcineurin inhibitors - mainly ciclosporin and tumor necrosis factor α (TNFα) antagonists have been shown to be viable therapeutic options to avoid colectomy in this scenario.

Research motivation

In contrast to that of ciclosporin, the performance of the calcineurin inhibitor tacrolimus in the clinical setting of steroid-refractory ulcerative colitis is insufficiently elucidated, but nonetheless recommended in national and international treatment guidelines for ulcerative colitis.

Research objectives

The objective of our study was to extend the current knowledge on the use of tacrolimus in steroid-refractory ulcerative colitis by assessing the short- and long-term outcomes of tacrolimus in adult inpatients suffering from steroid-refractory acute severe ulcerative colitis.

Research methods

We conducted a retrospective monocentric study enrolling 22 patients at a tertiary care center for the treatment of inflammatory bowel diseases. All patients who were admitted to one of the wards of the Department of Gastroenterology and Hepatology of the Heidelberg University Hospital with acute severe ulcerative colitis between 2007 and 2018 and who received oral or intravenous tacrolimus for steroid-refractory disease were included. Baseline characteristics and data on the disease courses were obtained from entirely computerized patient charts. The key study endpoints were clinical response to tacrolimus therapy, colectomy rate, time to colectomy and the occurrence of side effects.

Research results

Our study revealed that intravenous or oral tacrolimus, as in previous studies by other authors ciclosporin and infliximab, was able to prevent emergency colectomy in the majority of adult inpatients with steroid-refractory acute severe ulcerative colitis. At the same time, the safety profile of high-dose tacrolimus in this setting was acceptable. However, colectomy rates due to therapy-refractory disease courses over the year following tacrolimus rescue therapy reached nearly one-third of the patients. These results are also comparable to those of other studies dealing with the use of ciclosporin or infliximab in steroid-refractory acute severe ulcerative colitis.

Research conclusions

In all, tacrolimus appears to be a viable option for short-term treatment of steroid-refractory acute severe ulcerative colitis besides ciclosporin and anti-TNFα treatment.

Research perspectives

Even though not recommended for long-term maintenance therapy in ulcerative colitis, tacrolimus is a valuable tool for the short-term treatment of steroid-refractory severe ulcerative colitis, where rapid induction of symptom relief is warranted to gain time for the introduction of other, more slowly acting substances, with more favorable long-term toxicity profiles. Prospective trials are required to define its role among other medications, and to examine the safety of an overlapping combined use with these medications.