A Comprehensive Review on Immune Checkpoint Inhibitor-induced Colitis

Abstract

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target down-regulators of the anti-cancer immune response: Cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1, and its ligand programmed death-ligand 1. IMC is one of the most common adverse effects associated with checkpoint inhibitors.  The immune system has an important role in recognizing and eliminating tumors.

ICIs also transformed the treatment of a wide range of cancers. However, several immune-related adverse effects have been recorded, most of which occur when the immune system becomes less inhibited and affect various organs, including the gastrointestinal tract, causing diarrhoea and colitis. The incidence of immune-mediated colitis (IMC) ranges from 1%-25% depending on the type of ICI and if used in combination. Endoscopically and histologically there is a significant overlap between IMC and inflammatory bowel disease, however more neutrophilic inflammation without chronic inflammation is usually present in IMC. Corticosteroids are recommended for grade 2 or more severe colitis while holding the immunotherapy. Infliximab helps between one-third to two-thirds of patients who are steroid refractory. Vedolizumab has recently been shown to be effective in steroid and infliximab-resistant situations. If immunotherapy is permanently stopped in grade 4 colitis, the decision in grade 3 colitis is debatable.