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

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-refrac-tory 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.

Refractory Immune Checkpoint Inhibitor-Induced Colitis Improved by Tacrolimus: A Case Report

“…If the treatment described above achieves no improvement, then administration of biological preparations should also be considered. Several reports of studies have described the efficacy of IFX and VDZ against ICI-induced colitis [ 19 , 20 , 21 , 22 ]. According to earlier reports, many cases of ICI-induced colitis were improved by the treatment described above [ 15 ].…”

Flexible sigmoidoscopy may be sufficient for initial evaluation of suspected immunotherapy‐mediated colitis: A cross‐sectional study

“…Although a number of studies 5,6,13,[17][18][19] have described the yield of lower GI endoscopy for diagnosing IMC, few have correlated endoscopic abnormalities with the presence of histologic evidence of IMC in the same segment of colon. In our study, 93.8% of left-sided colon biopsies with abnormal endoscopic appearance and 68.6% of left-sided colon biopsies of normal-appearing mucosa had histological evidence of IMC.…”

“…Recent guidelines 5,8 state that endoscopy with biopsies are vital for diagnosing IMC, as high-risk endoscopic features such as pancolitis and deep ulceration are associated with steroid refractory colitis. 5,6,23 Other studies have proposed the use of endoscopic and histological scoring systems (such as the Mayo Endoscopic Score) to determine treatment duration and the need for infliximab. 18,19 Full colonoscopy may be required to assess the entire colon for these high-risk features, however, because isolated right colonic gross abnormalities were rare and isolated histologic evidence of IMC were absent in our cohort, the use of flexible sigmoidoscopy may be sufficient to guide treatment in Two patients had right hemicolectomy, 1 out of 2 had evidence of ICI in their transverse and left colon while the other had no evidence of ICI in these segments.…”

“…However, studies have shown that CTCAE criteria for colitis and diarrhea alone may not accurately predict IMC severity and prognosis. 3,4 The role of endoscopy in diagnosing and assessing IMC severity has been studied 5,6 and, according to recent guidelines, 5,7 lower endoscopy with biopsy is considered the gold standard for diagnosing IMC in addition to ruling out alternative diagnoses. Nevertheless, the optimal lower endoscopic strategy (full colonoscopy or a limited flexible sigmoidoscopy) for obtaining biopsies and assessing severity of mucosal damage remains unclear.…”

Systematic review: disease activity indices for immune checkpoint inhibitor‐associated enterocolitis

“…Four studies assessed the operating properties of the CTCAE. [24][25][26][27] The CTCAE has been evaluated for criterion and construct validity, and feasibility with mixed results. One study found a negative correlation between diarrhoea grade and biomarkers of disease activity, while another study found a positive relationship between diarrhoea grade and biomarkers.…”