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

Acute severe ulcerative colitis unresponsive to systemic steroid treatment is a life-threatening medical condition requiring hospitalization and often colectomy. Despite the increasing choice of medical therapy options for ulcerative colitis, the condition remains a great challenge in the field of inflammatory bowel diseases (IBD). The performance of the calcineurin inhibitor tacrolimus in this clinical setting is insufficiently elucidated.


To evaluate the short and long-term outcomes of tacrolimus therapy in adult inpatients with steroid-refractory acute severe ulcerative colitis.


We conducted a retrospective monocentric study enrolling 22 patients at a tertiary care center for the treatment of IBD. 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 retrieved from entirely computerized patient charts. The primary study endpoint was clinical response to tacrolimus therapy, resulting in discharge from the hospital. Secondary study endpoints were colectomy rate and time to colectomy, achievement of clinical remission under tacrolimus therapy, and the occurrence of side effects.


In the majority of the 22 included patients (68.2%), tacrolimus therapy was initiated intravenously and subsequently converted to oral administration. The treatment duration was 128 ± 28.5 d (mean ± SEM), and the patients were followed up for 705 ± 110 d after treatment initiation. Among all patients, 86.4% were discharged from the hospital under continued oral tacrolimus therapy. In 36.4% of the patients, the administration of tacrolimus resulted in clinical remission at some point during the treatment. Thirty-two percent of the patients underwent colectomy between 5 and 194 d after the initiation of tacrolimus treatment (mean: 97.4 ± 20.8 d). Colectomy-free survival rates at 1, 3, 6 and 12 mo after the initiation of tacrolimus therapy were 90.9%, 86.4%, 77.3% and 68.2%, respectively. The safety profile of tacrolimus was overall favorable. Only two patients discontinued the treatment due to side effects.


The short-term outcome of tacrolimus in steroid-refractory acute severe ulcerative colitis was beneficial, and side effects were rare. In all, tacrolimus therapy appears to be a viable option for short-term treatment of steroid-refractory acute severe ulcerative colitis besides ciclosporin and anti-tumor necrosis factor α treatment.

Keywords: Acute severe ulcerative colitis, Steroid-refractory, Tacrolimus, Rescue therapy, Calcineurin inhibitor, Inflammatory bowel disease, Hospitalized

Core tip: Steroid-refractory acute severe ulcerative colitis requires hospitalization and is frequently a risky tightrope walk between surgery and medical treatment. Whereas sufficient data has been provided over time to justify ciclosporin and infliximab as salvage therapies in this clinical scenario, guideline recommendations are still more reluctant towards tacrolimus due to the relative lack of data. However, tacrolimus may have advantages over ciclosporin especially due to its different toxicity profile. Our study provides more insight in the potential of tacrolimus in the strictly defined situation of steroid-refractory acute severe ulcerative colitis in hospitalized patients.