Checkpoint Inhibitor-Induced Colitis: An Update

Abstract

Immunotherapy with immune checkpoint inhibitors (ICIs) nowadays has indications for several solid tumors. The current targets for ICIs are CTLA-4, PD-1, and PD-L1 receptors. Despite the clinical advantages derived from ICIs, a variety of side effects are linked to overstimulation of the immune system. Among these, ICI-related colitis is one of the most common, with a disabling impact on the patient. Diarrhea, abdominal pain, abdominal distension, cramping, and hematochezia are the most common ICI enterocolitis presenting symptoms. The most frequently used grading system for assessment of the severity of ICI enterocolitis is called the Common Terminology Criteria for Adverse Events (CTCAE) grading. With regard to the histological picture, there is no specific feature; however, microscopic damage can be classified into five types: (1) acute active colitis, (2) chronic active colitis, (3) microscopic colitis-like, (4) graft-versus-host disease-like, and (5) other types. Supportive therapy (oral hydration, a bland diet without lactose or caffeine, and anti-diarrheal agents) is indicated in mild colitis. Symptomatic treatment alone or with loperamide, a low-fiber diet, and spasmolytics are recommended for low-grade diarrhea. In more severe cases, corticosteroid treatment is mandatory. In refractory cases, off-label use of biological therapies (infliximab or vedolizumab) was proposed.

Outcome of an Accelerated Treatment Algorithm for Patients Developing Diarrhea as a Complication of Ipilimumab-Based Cancer Immunotherapy in a Community Practice

“…The median time to resolution of diarrhea from the first infliximab dose was 8.5 ± 16.4 days. Other studies have also demonstrated a similarly high clinical remission rate (87%) following the addition of infliximab to steroids for immune-mediated diarrhea [ 35 ].…”

PD-L1 Restrains the PD-1hiNrp1loTGFβ+Treg to block IL6+Neutrophil tumor infiltration to Suppress Inflammation-driven Colorectal Cancer

“…PD-L1 protein inhibits colonic inflammation and colitis in mice 24 . A major adverse effect of PD-(L)1 ICI immunotherapy in human cancer patients is ulcerative colitis 22,38–41 . PD-L1 therefore plays an essential role in protecting colorectal epithelium from colonic inflammation.…”

Occurrence of Fatal Tubulopathy in an Old, Fit Patient Receiving Nivolumab and Ipilimumab for Metastatic Melanoma: A Case Report

“…Off-label use of infliximab and vedolizumab has been associated with good clinical responses. This patient reported not having a good response to Infliximab, but vedolizumab seemed effective on gastrointestinal symptoms [ 11 ].…”