Immune checkpoint inhibitor-associated gastrointestinal and hepatic adverse events and their management

Uday N Shivaji; Louisa Jeffery; Xianyong Gui; Samuel C L Smith; Omer F Ahmad; Ayesha Akbar; Subrata Ghosh; Marietta Iacucci

doi:10.1177/1756284819884196

Immune checkpoint inhibitor-associated gastrointestinal and hepatic adverse events and their management

Therap Adv Gastroenterol. 2019 Nov 5:12:1756284819884196. doi: 10.1177/1756284819884196. eCollection 2019.

Authors

Uday N Shivaji¹, Louisa Jeffery¹, Xianyong Gui², Samuel C L Smith³, Omer F Ahmad⁴, Ayesha Akbar⁵, Subrata Ghosh¹, Marietta Iacucci¹

Affiliations

¹ National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, UK.
² Department of Pathology, University of Washington, Seattle, WA, USA.
³ Institute of Immunology and Immunotherapy, University of Birmingham, UK.
⁴ Department of Gastroenterology, University College London Hospital, London, UK.
⁵ St Mark's Hospital, IBD Unit, London, UK.

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.

Keywords: anti-CTLA-4; anti-PD1; anti-PDL1; immune checkpoint inhibitors; immune-related colitis; immune-related hepatitis; management.

Publication types

Review