Retrospective Analysis of Treatment and Complications of Immune Checkpoint Inhibitor-Associated Colitis: Histological Ulcerations as Potential Predictor for a Steroid-Refractory Disease Course

Inflamm Intest Dis. 2020 Aug;5(3):109-116. doi: 10.1159/000507579. Epub 2020 May 26.

Abstract

Background/aims: Among the severe immune-related adverse events (irAEs) that occur with immune checkpoint inhibitor (ICI) therapy, colitis is the most frequent one. This study aimed at describing the experience from the largest gastroenterology unit in Switzerland with immune checkpoint inhibitor-associated colitis (ICIAC), its clinical presentation, management, and outcomes.

Methods: We performed a retrospective review of patients who were referred for the evaluation of ICIAC between January 2011 and October 2018 to the Division of Gastroenterology and Hepatology, University Hospital Zurich.

Results: Thirty-three patients with immune-related colitis grade 3 or 4 met the inclusion criteria and were analyzed in detail: All patients had diarrhea, 64% had abdominal pain, 42% had bloody stool, 27% had emesis, and 18% developed fever. In total, 33% were successfully treated with corticosteroids alone; 66% were steroid-refractory and treated with infliximab or vedolizumab. Two of these patients developed severe complications requiring surgery. All patients reached complete remission of ICIAC and its symptoms. At colonoscopy, ulcerations were seen in 37% of steroid-refractory versus 63% of steroid-responsive cases. Deep histological ulcerations invading the submucosa were only present in steroid-refractory cases.

Conclusion: ICIAC is a severe irAE which frequently requires high-dose steroids and a close follow-up due to deleterious complications. The detection of histologically diagnosed deep ulcerations may predict a steroid-refractory course and may warrant early application of infliximab. However, larger studies are required to confirm our findings.

Keywords: Histology; Infliximab; Malignant melanoma; Nivolumab; Vedolizumab.