Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2019; 25(31): 4481-4492
Published online Aug 21, 2019. doi: 10.3748/wjg.v25.i31.4481
Ustekinumab: “Real-world” outcomes and potential predictors of nonresponse in treatment-refractory Crohn’s disease
Peter Hoffmann, Johannes Krisam, Cyrill Wehling, Petra Kloeters-Plachky, Yvonne Leopold, Nina Belling, Annika Gauss
Peter Hoffmann, Cyrill Wehling, Petra Kloeters-Plachky, Yvonne Leopold, Nina Belling, Annika Gauss, Department of Gastroenterology and Hepatology, University Hospital Heidelberg, Heidelberg 69120, Germany
Johannes Krisam, Department of Medical Biometry, University Hospital Heidelberg, Heidelberg 69120, Germany
Author contributions: Hoffmann P and Gauss A designed research, performed research and wrote the paper; Krisam J analysed data; Kloeters-Plachky P and Leopold Y helped perform research and analysed data; Belling N and Wehling C performed research.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Heidelberg.
Informed consent statement: For NOD2 genotyping, written informed consent was necessary. For the retrospective analysis there was no informed consent required according to the Ethics Committee of Heidelberg.
Data sharing statement: No additional data are available.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Peter Hoffmann, MD, Doctor, Department of Gastroenterology and Hepatology, University Hospital Heidelberg, Im Neuenheimer Feld 410, Heidelberg 69120, Germany. peter.hoffmann@med.uni-heidelberg.de
Telephone: +49-6221-5636422 Fax: +49-6221-565255
Received: May 9, 2019
Peer-review started: May 10, 2019
First decision: June 16, 2019
Revised: July 9, 2019
Accepted: July 19, 2019
Article in press: July 19, 2019
Published online: August 21, 2019
Processing time: 104 Days and 16 Hours
Abstract
BACKGROUND

Ustekinumab was approved in Europe for the treatment of adults with moderate to severe Crohn's disease (CD) in 2016, and there is an urgent need for data on its everyday use.

AIM

To obtain data on the daily use of ustekinumab.

METHODS

This is a retrospective monocentric study. Patients with moderate to severe CD who began ustekinumab therapy at the inflammatory bowel diseases outpatient clinic of the Heidelberg University Hospital between December 2016 and March 2018 were selected based on electronic patient files. The primary study endpoint was combined steroid-free clinical remission or steroid-free clinical response at 24 ± 6 wk of ustekinumab therapy. Secondary study endpoints were: achievement of mucosal healing, sonographic and magnetic resonance imaging response, biochemical response, the need for intestinal surgery within 24 ± 6 wk after treatment initiation, the occurrence of adverse events, treatment discontinuation due to nonresponse or adverse events, improvement of extraintestinal manifestations, clinical response at 48 ± 6 wk of therapy, and association of response with nucleotid oligodimerisation domain 2 mutations.

RESULTS

Fifty-seven patients with CD (5.3% anti-tumour necrosis factor α naïve, 63.2% having undergone at least one intestinal surgery) were included in the study. Twenty patients (35.1%) achieved steroid-free clinical remission, 6 (10.5%) steroid-free clinical response and 31 (54.4%) were non-responders. Treatment discontinuation due to adverse events occurred in two patients (3.5%). Male sex, the presence of extraintestinal manifestations and the use of steroids at baseline were predictors of nonresponse to ustekinumab therapy.

CONCLUSION

In a “real-world” treatment-refractory cohort of patients with CD, ustekinumab appeared efficacious and safe.

Keywords: Eeal-world; Ustekinumab; Crohn’s disease

Core tip: Real-world data on ustekinumab in Crohn's disease (CD) are scarce. This is a retrospective monocentric study. Patients with CD who began ustekinumab therapy at a tertiary referral centre between 2016 and 2018 were included. The primary study endpoint was combined steroid-free clinical remission or response at 24 ± 6 wk of ustekinumab therapy. Fifty-seven patients were included in the study. Twenty patients (35.1%) achieved remission and 6 (10.5%) achieved a clinical response. Male sex, extraintestinal manifestations and the use of steroids at baseline were predictors of nonresponse to ustekinumab therapy. In a “real-world” treatment-refractory cohort of patients with CD, ustekinumab appeared efficacious and safe.