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Checkpoint inhibitor colitis: a new model of inflammatory bowel disease?
Spyros I Siakavellas1, Giorgos Bamias
1Gastroenterology Unit, Third Academic Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Sotiria Hospital, Athens, Greece.
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.
Insights
Immune checkpoint inhibitor colitis (CIC) shares similarities with inflammatory bowel disease (IBD) but is a distinct condition. Understanding CIC pathogenesis and treatment is crucial for managing immune-mediated colitides.
Area of Science:
- Oncology
- Immunology
- Gastroenterology
Background:
- Immune checkpoint inhibitors (ICIs) targeting CTLA-4 and PD-1/PD-L1 are used in cancer therapy.
- ICI use is linked to immune-related adverse events, notably colitis.
- Checkpoint inhibitor colitis (CIC) clinically and endoscopically resembles inflammatory bowel disease (IBD).
Purpose of the Study:
- To review recent developments in checkpoint inhibitor colitis (CIC).
- To compare CIC characteristics with inflammatory bowel disease (IBD).
- To discuss the pathogenesis and treatment of CIC.
Main Methods:
- Review of patient cohorts with CIC.
- Clinical, endoscopic, and histological comparison with IBD.
- Analysis of immunopathogenesis and treatment strategies.
Main Results:
- CIC shows significant overlap with IBD in clinical and endoscopic features.
- Histology of CIC can mimic IBD or lymphocytic colitis.
- CIC immunopathogenesis involves Th1/Th17 responses and gut microbiota.
- Steroids and infliximab are current treatments; vedolizumab may also be effective.
Conclusions:
- CIC is a distinct colitis with IBD-like features.
- Further research into CIC pathogenesis will improve management of immune-mediated colitides.
- Clarifying CIC mechanisms aids understanding and treatment of IBD.
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