Immune-Mediated upper gastrointestinal toxicities reported With immune checkpoint inhibitors: An analysis of the food and drug administration adverse event reporting system (FAERS)

Abstract

Purpose

This study aimed to characterize FAERS reports of immune-mediated upper gastrointestinal (GI) toxicities associated with immune checkpoint inhibitors and to explore disproportional reporting patterns across ICI classes and treatment regimens.

Methods

Input data were downloaded from the public release of the FDA database including time period between January 1 2016, and December 31, 2024. 132 patients with upper-GI toxicity were included. Categorical variables were compared using either the chi-square test or Fisher's exact test. To evaluate the potential association between ICIs and specific upper-GI toxicity events of interest, a disproportionality analysis was conducted using the Reporting Odds Ratio (ROR) method. A signal was considered statistically significant when the lower bound of the 95% confidence interval for the ROR exceeded 1.0.

Results

Anti-PD-1 agents showed higher disproportional reporting of upper-GI toxicities compared to anti-PD-L1 (p = 0.001, ROR = 3.83 95% CI: 1.53–15.23). A higher proportion of hospitalization among reported cases were observed in patients treated with concurrent chemotherapy, compared to those did not receive chemotherapy (ROR = 2.5; 95% CI: 1.05–5.921; p = 0.045).

Conclusion

Anti-PD-1 therapy showed a stronger reporting signal for upper-GI toxicity than anti-PD-L1 therapy in FAERS, although the number of anti-PD-L1 cases was small. Concurrent chemotherapy was associated with a higher proportion of hospitalization among reported cases. These findings are exploratory and hypothesis-generating.