Gastrointestinal adverse events associated with immune checkpoint inhibitors: a pharmacovigilance analysis of the EudraVigilance and VigiAccess databases.

Abstract

Background: This study aimed to provide an overview of gastrointestinal (GI) adverse events associated with immune checkpoint inhibitors (ICIs) using two pharmacovigilance databases, EudraVigilance and VigiAccess.

Research design and methods: Data was collected from the date of ICI's marketing authorization until 30 November 2023. Reporting odds ratio (ROR) was used as a measure of ADR reporting disproportionality for signal detection.

Results: Overall, across both databases, EudraVigilance and VigiAccess, a total of 76,606 ADR reports were analyzed. In EudraVigilance, colitis (12,581) and diarrhea (12,108) were the most reported GI adverse events, with similar findings in VigiAccess. Furthermore, in both databases, the most ADR reports were associated with nivolumab and pembrolizumab. Durvalumab (ROR:3.96,95%CI:3.65-4.28), ipilimumab (ROR:1.95,95%CI:1.89-2.01), nivolumab (ROR:1.05,95%CI:1.02-1.07), and atezolizumab (ROR:1.04,95%CI:1.01-1.07) demonstrated higher risks of GI events compared to other ICIs. EudraVigilance analysis identified dysphagia, ascites, hematochezia, and gastroesophageal reflux disease as potential signals associated with ICI therapy. Majority of ADR reports (87.2%) comprised serious GI adverse events, a portion of which was associated with fatal outcomes (14.5%). Atezolizumab (14.9%) and pembrolizumab (11.9%) were linked to a higher incidence of fatal outcomes compared to other ICIs.

Conclusion: The differential risk profiles of ICIs-associated-GI adverse events underscore the importance of personalized therapy in oncology.