eprintid: 10086609
rev_number: 17
eprint_status: archive
userid: 608
dir: disk0/10/08/66/09
datestamp: 2019-11-26 17:54:56
lastmod: 2021-09-23 22:39:42
status_changed: 2019-11-26 17:54:56
type: article
metadata_visibility: show
creators_name: Shivaji, UN
creators_name: Jeffery, L
creators_name: Gui, X
creators_name: Smith, SCL
creators_name: Ahmad, OF
creators_name: Akbar, A
creators_name: Ghosh, S
creators_name: Iacucci, M
title: Immune checkpoint inhibitor-associated gastrointestinal and hepatic adverse events and their management
ispublished: pub
subjects: UCH
divisions: UCL
divisions: B04
divisions: C05
divisions: F42
keywords: anti-CTLA-4, anti-PD1, anti-PDL1, immune checkpoint inhibitors, immune-related hepatitis, immune-related colitis, management
note: © 2019 by SAGE Publications Ltd. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/).
abstract: BACKGROUND: Drug-induced colitis is a known complication of therapies that alter the immune balance, damage the intestinal barrier or disturb intestinal microbiota. Immune checkpoint inhibitors (ICI) directed against cancer cells may result in activated T lymphocyte-induced immune-related adverse events (AEs), including immune-related colitis and hepatitis. The aim of this review article is to summarize the incidence of gastrointestinal (GI) and hepatic AEs related to ICI therapy. We have also looked at the pathogenesis of immune-mediated AEs and propose management strategies based on current available evidence. METHODS: A literature search using PubMed and Medline databases was undertaken using relevant search terms pertaining to names of individual drugs, mechanism of action, related AEs and their management. RESULTS: ICI-related GI AEs are common, and colitis appears to be the most common side effect, with some studies reporting incidence as high as 30%. The incidence of both all-grade colitis and hepatitis were highest with combination therapy with anti-CTLA-4/PD-1; severity of colitis was dose-dependent (anti-CTLA-4). Early intervention is associated with better outcomes. CONCLUSION: ICI-related GI and hepatic AEs are common and clinicians need to be aware. Patients with GI AEs benefit from early diagnosis using endoscopy and computed tomography. Early intervention with oral steroids is effective in the majority of patients, and in steroid-refractory colitis infliximab and vedolizumab have been reported to be useful; mycophenolate has been used for steroid-refractory hepatitis.
date: 2019-01
date_type: published
official_url: https://doi.org/10.1177%2F1756284819884196
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1720886
doi: 10.1177/1756284819884196
lyricists_name: Ahmad, Omer
lyricists_id: OFAHM68
actors_name: Flynn, Bernadette
actors_id: BFFLY94
actors_role: owner
full_text_status: public
publication: Therapeutic Advances in Gastroenterology
volume: 12
pagerange: 1-15
issn: 1756-2848
citation:        Shivaji, UN;    Jeffery, L;    Gui, X;    Smith, SCL;    Ahmad, OF;    Akbar, A;    Ghosh, S;           Shivaji, UN;  Jeffery, L;  Gui, X;  Smith, SCL;  Ahmad, OF;  Akbar, A;  Ghosh, S;  Iacucci, M;   - view fewer <#>    (2019)    Immune checkpoint inhibitor-associated gastrointestinal and hepatic adverse events and their management.                   Therapeutic Advances in Gastroenterology , 12    pp. 1-15.    10.1177/1756284819884196 <https://doi.org/10.1177/1756284819884196>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10086609/1/1756284819884196.pdf