Checkpoint Inhibitor-Induced Colitis: A New Type of Inflammatory Bowel Disease?

Abstract

Checkpoint inhibitors are immune-stimulatory antibodies that have transformed the management and prognosis of individuals with metastatic melanoma and other cancers. Checkpoint inhibitor–induced colitis is an increasingly recognized immune-related adverse event that shares many of the same phenotypical, serological, and histological characteristics of both Crohn’s disease and ulcerative colitis, suggesting that checkpoint inhibitor–induced colitis may represent a new inflammatory bowel disease phenotype. We report a 73-year-old man with metastatic melanoma who developed ipilimumab-induced colitis with subsequent transformation to Crohn?s colitis-like phenotype after the addition of pembrolizumab.

Morphological spectrum of immune check‐point inhibitor therapy‐associated gastritis

“…A 73‐year‐old man with prostate cancer and malignant melanoma on ipilimumab developed a severe colitis that did not completely respond to steroid therapy, and when treated with infliximab the patient developed a hypersensitivity reaction. The severity of colitis led to treatment with a different anti‐TNF agent, adalimumab, along with an immunomodulator, methotrexate, similar to guidelines used for IBD patients, which led to resolution of symptoms . Moreover, anti‐CTLA‐4 colitis has also been previously shown to lead to the development of serological markers associated with IBD, such as pANCA and anti‐Omp3, often concurrently, which is unusual for typical IBD patients .…”

Intestinal development and homeostasis require activation and apoptosis of diet-reactive T cells

“…Interestingly, in the absence of IL-10, blocking of PD-1 favored development of colitis in these mice. Numerous reports show that colitis development remains a complication after treatment of cancer patients with an anti-PD-1 checkpoint inhibitor (43)(44)(45).…”

Les limites des inhibiteurs de points de contrôle immunitaire et la gestion de leur toxicité

“…Après leurs résultats spectaculaires dans le mélanome métastatique, puis dans les cancers du poumon inopérables, les cancers du rein et urothéliaux, certains cancers digestifs, certains lymphomes, plus d'une centaine d'essais cliniques sont actuellement en cours et l'utilisation des ICI est devenue l'une des stratégies thérapeutiques la plus prometteuse en oncologie. L'obtention d'une réponse tumorale stable, voire la rémission d'un cancer métastatique, se font souvent au prix d'une toxicité immunologique pouvant concerner La révolution des anticorps modulateurs de la réponse immunitaire en oncologie inflammatoires peuvent survenir, identiques à celles observées dans la maladie de Crohn ou les colites microscopiques [8]. Elles mettent en jeu le pronostic vital du patient en raison du risque de perforation intestinale.…”