Incident reporting and outcomes of gastrointestinal adverse events with immune checkpoint inhibitors.

Abstract

e14663 Background: Immune checkpoint inhibitor therapies act by blocking inhibitory molecules involved in the regulation of T cells, thus releasing tumor-specific T cells to destroy their tumor targets. However, immune checkpoint inhibitors (ICI) can also lead to a breach in self-tolerance, resulting in immune-related adverse events (irAEs) that include tissue-specific autoimmunity. Gastrointestinal side effects are not an exception. However, large-scale data is lacking given the rarity of these events. We aimed to analyze these rare gastrointestinal adverse effects in patients taking immune checkpoint inhibitors using the Food and Drug Adverse Event Reporting (FAERS) database. Methods: We employed the FAERS and the Medical Dictionary for Regulatory Activities (MEDRA) database, a publicly available dashboard, to conduct this retrospective pharmacovigilance study. We analyzed the incident reporting gastrointestinal side effects with ICIs. The five most commonly used ICIs (Pembrolizumab, Nivolumab, Durvalumab, Atezolizumab, and Ipilimumab) were taken into our analysis. The public dashboard of the database was approached on 11/30/2024. Drugs were searched by the “Search by product” bar and reactions were categorized. Outcomes reported as Hospitalization, Death, or life-threatening events. Results: A total of 2,24,889 AEs were associated with ICIs out of which, 20% (n = 45088) were related to GI-AEs. The highest proportion of GI-AEs were reported with ipilimumab and the lowest is with Durvalumab. Most cases were reported in the > 65 age group (41.5%), with a significant portion also observed in the 18-64 age group (36%). GI adverse events were predominantly reported in men except for pembrolizumab in which the adverse events were more reported in women. Healthcare professionals reported most of the adverse event’s accounting for 81.64% of cases across all the agents compared to 17.9% reported by the consumer. 65.42% of the total cases were reported outside the USA compared to 34.56% reported in the USA. 56.51% of the total cases across all agents were hospitalized with deaths reported in 16.2% of the total cases. Colitis contributed to 13.9% of the total adverse events across all the agents with immune-mediated enterocolitis being 6.07%. Conclusions: In our large database study, we have found that GI side effects constitute 20% of total adverse events reported. Immune-mediated colitis constitutes 13% of the total adverse events with very high mortality rates. Large-scale prospective studies are needed to decipher this entity and identify strategies to prevent these events in patients on ICIs.