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World J Clin Cases. Feb 26, 2019; 7(4): 405-418
Published online Feb 26, 2019. doi: 10.12998/wjcc.v7.i4.405
Immune checkpoint inhibitor-induced colitis: A comprehensive review
Aniruddh Som, Rohan Mandaliya, Dana Alsaadi, Maham Farshidpour, Aline Charabaty, Nidhi Malhotra, Mark C Mattar
Aniruddh Som, Department of Internal Medicine, Medstar Washington Hospital Center, Washington, DC 20010, United States
Rohan Mandaliya, Mark C Mattar, Department of Gastroenterology, MedStar Georgetown University Hospital, Washington, DC 20007, United States
Dana Alsaadi, Department of Internal Medicine, MedStar Georgetown University Hospital, Washington, DC 20007, United States
Maham Farshidpour, Department of Internal Medicine, MedStar Union Memorial Hospital and Good Samaritan Hospital, Baltimore, MD 21218, United States
Aline Charabaty, Department of Gastroenterology, Sibley Memorial Hospital, Washington, DC 20007, United States
Nidhi Malhotra, Department of Gastroenterology, MedStar Washington Hospital Center, Washington, DC 20010, United States
Author contributions: All authors contributed to this paper.
Conflict-of-interest statement: None.
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: Mark C Mattar, FACG, MD, Attending Doctor, Gastroenterology Fellowship Program Director, Director of IBD Center, Department of Gastroenterology, MedStar Georgetown University Hospital, 3800 Reservoir Rd NW, Washington, DC 20007, United States. mark.c.mattar@medstar.net
Telephone: +1-202-4441039
Received: September 21, 2018
Peer-review started: September 21, 2018
First decision: October 16, 2018
Revised: January 21, 2019
Accepted: January 26, 2019
Article in press: January 26, 2019
Published online: February 26, 2019
Abstract

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target down-regulators of the anti-cancer immune response: Cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1, and its ligand programmed death-ligand 1. ICIs have revolutionized the treatment of a variety of malignancies. However, many immune-related adverse events have also been described which mainly occurs as the immune system becomes less suppressed, affecting various organs including the gastrointestinal tract and causing diarrhea and colitis. The incidence of immune-mediated colitis (IMC) ranges from 1%-25% depending on the type of ICI and if used in combination. Endoscopically and histologically there is a significant overlap between IMC and inflammatory bowel disease, however more neutrophilic inflammation without chronic inflammation is usually present in IMC. Corticosteroids are recommended for grade 2 or more severe colitis while holding the immunotherapy. About one third to two thirds of patients are steroid refractory and benefit from infliximab. Recently vedolizumab has been found to be efficacious in steroid and infliximab refractory cases. While in grade 4 colitis, the immunotherapy is permanently discontinued, the decision is controversial in grade 3 colitis.

Keywords: Immune checkpoint inhibitors, Immune-related adverse events, Cytotoxic T-lymphocyte-associated antigen 4, Programmed cell death protein 1, Programmed death-ligand 1, Immune-mediated colitis

Core tip: Immune-mediated colitis (IMC) is a common immune related adverse event associated with immune checkpoint inhibitors. It typically occurs 5 wk-10 wk after the 2nd or 3rd dose of treatment. Endoscopically, it is indistinguishable from inflammatory bowel disease with significant overlap in histology. Optimal management of IMC requires early recognition and timely use of corticosteroids. About one third to two thirds of patients are steroid refractory. Infliximab is the second line therapy in these patients. Recent reports have shown that Vedolizumab is more gut specific and efficacious in steroid and infliximab refractory cases. Fecal microbiota transplant has recently been reported to be successful in steroid refractory cases.