Simon Pernot1, Toulsie Ramtohul, Julien Taieb. 1. Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris Descartes University, Paris, France.
Abstract
PURPOSE OF REVIEW: Recent development of checkpoint inhibitors is a challenge for oncologists. Indeed, it leads to specific immune adverse events, close to autoimmune disorders, which require a specific management. Colitis is one of the most frequent immune adverse events, in particular with anticytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) therapy. RECENT FINDINGS: Severe colitis is frequent with immune checkpoint inhibitors and leads in a few cases to bowel perforation and death. This review focuses on specific pathogenic pathway and recent findings on risk factors and managements of colitis. SUMMARY: Anti-CTLA-4 antibodies are the most involved immune checkpoint inhibitors in colitis, and the combinations with anti-programmed death ligand 1 dramatically increase the rate of colitis. The early use of budesonide, and in some cases corticosteroids and/or infliximab should be recommended, as colitis is responsive to infliximab in almost all cases. Immune-related colitis shares some characteristics with inflammatory bowel disease but with little specificity. In particular, it has been recently showed that gut microbiota could interact with anti-CTLA-4 treatment to modulate efficacy but also to induce colitis. This opens the way for preventive or curative treatments capable of inducing modulation of the microbiota or fecal transplantation.
PURPOSE OF REVIEW: Recent development of checkpoint inhibitors is a challenge for oncologists. Indeed, it leads to specific immune adverse events, close to autoimmune disorders, which require a specific management. Colitis is one of the most frequent immune adverse events, in particular with anticytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) therapy. RECENT FINDINGS: Severe colitis is frequent with immune checkpoint inhibitors and leads in a few cases to bowel perforation and death. This review focuses on specific pathogenic pathway and recent findings on risk factors and managements of colitis. SUMMARY: Anti-CTLA-4 antibodies are the most involved immune checkpoint inhibitors in colitis, and the combinations with anti-programmed death ligand 1 dramatically increase the rate of colitis. The early use of budesonide, and in some cases corticosteroids and/or infliximab should be recommended, as colitis is responsive to infliximab in almost all cases. Immune-related colitis shares some characteristics with inflammatory bowel disease but with little specificity. In particular, it has been recently showed that gut microbiota could interact with anti-CTLA-4 treatment to modulate efficacy but also to induce colitis. This opens the way for preventive or curative treatments capable of inducing modulation of the microbiota or fecal transplantation.
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