Effect of Acid Suppressants on Adverse Events of Immune Checkpoint Inhibitors Using Real-world Databases

Immune checkpoint inhibitors (ICIs) cause immune-related adverse events (irAEs) in various organs. Although many studies have suggested that acid suppressants (ASs) may affect irAEs, limited sample sizes have hindered detailed evaluations. Therefore, this study aimed to assess the impact of ASs on individual irAEs using large real-world databases, the Japanese Adverse Drug Event Report database (JADER) and the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).

We analyzed adverse event (AE) reports from the JADER and FAERS databases to assess the impact of ASs on ICI-related AEs. Reporting odds ratios (RORs) and 95% confidence intervals (95%CI) were calculated. Drug-drug interaction signals were defined by non-overlapping 95%CIs between ICIs alone and their combination use.

Co-administration with ASs or proton pump inhibitors (PPIs) was associated with an increased risk of acute kidney injury (AKI) in both datasets, while H2-receptor antagonists (H2RAs) showed weaker or no signals. The incidence of endocrine-related AEs tended to decrease with ASs. The colitis results differed between the two datasets, with a decreased incidence in the JADER and an increased incidence in FAERS. Other ICI-related AEs showed consistent trends across datasets. Subgroup analyses of individual PPIs revealed varying results for AKI and colitis between the JADER and FAERS databases, with no consistent trends across PPIs.

ASs have diverse effects on ICI-induced AEs and their characteristics may differ between PPIs and H2RAs.