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Checkpoint inhibitor colitis

a new model of inflammatory bowel disease?

Siakavellas, Spyros I.; Bamias, Giorgos

Current Opinion in Gastroenterology: November 2018 - Volume 34 - Issue 6 - p 377–383
doi: 10.1097/MOG.0000000000000482
IMMUNOLOGY: Edited by Maria T. Abreu
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Purpose of review Immune checkpoint inhibitors are monoclonal antibodies against the inhibitory, co-stimulatory molecules CTLA-4 and PD-1/PD-L1. Their use in oncology has been associated with frequent and diverse immune-related adverse events. In the digestive tract, such toxicity presents primarily as colonic inflammation, resembling inflammatory bowel disease (IBD). This review presents recent developments regarding the characteristics of checkpoint inhibitor colitis (CIC) and its relation to IBD.

Recent findings Several reports from patient cohorts with CIC have outlined its similarities and differences with IBD. Clinically and endoscopically, there is high overlap, including the negative prognostic significance of deep ulceration. Histologically, CIC may present as either acute colitis or demonstrate features of chronic damage, including IBD-like and lymphocytic colitis-like phenotypes. CIC immunopathogenesis appears to be associated with a predominance of mucosal Th1/Th17 effector responses, and may also be influenced by input from the gut microflora. Finally, current treatment of CIC is based on steroids and infliximab, although other biologics such as vedolizumab may also be effective.

Summary CIC represents a distinct form of colitis with characteristics reminiscent of IBD flares. Clarification of the mechanisms involved in its pathogenesis will greatly enhance our understanding and therapeutic management of immune-mediated colitides, including IBD.

Gastroenterology Unit, Third Academic Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Sotiria Hospital, Athens, Greece

Correspondence to Giorgos Bamias, MD, PhD, Associate Professor of Gastroenterology, Gastroenterology Unit, Third Academic Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Sotiria Hospital, 152 Mesogion Avenue, 11527 Athens, Greece. Tel: +30 2107763297; e-mail: gbamias@gmail.com

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