Comprehensive safety analysis of the clinical spectrum of adverse events associated with immune checkpoint inhibitors based on FAERS.

Background: The toxicities associated with immune checkpoint inhibitors (ICIs) can affect nearly all organ systems. Although previous studies have examined specific types of immune-related adverse events (irAEs) associated with ICIs, comprehensive evaluations of the clinical profiles of irAEs using data from the FDA Adverse Event Reporting System database over an extended period have been lacking. Methods: Duplicate records and reports submitted by nonprofessionals were removed for data cleaning. Employing three disproportional statistical methods (Reporting Odds Ratio, Bayesian Confidence Propagation Neural Network, and Multi-Item Gamma Poisson Shrinker) with MedDRA version 27.1 classification, we identified and ranked adverse event signals across System Organ Class (SOC), Standardized MedDRA Query (SMQ), and Preferred Term (PT). Results: A total of 320,556 adverse event reports associated with eight ICIs, involving 123,210 patients, were included in the analysis. At the SOC level, endocrine disorders and hepatobiliary disorders exhibited the strongest signals, while cardiac and respiratory toxicities showed the highest mortality risks across vital organ systems. At the SMQ level, the most prominent signals included noninfectious encephalitis, hypothyroidism, noninfectious myocarditis/pericarditis, eosinophilic pneumonia, and interstitial lung disease. At the PT level, the leading signals were immune-mediated lung disease, immune-mediated enterocolitis, immune-mediated hepatitis, (immune-mediated) myocarditis, hypophysitis, and adrenal insufficiency. Conclusions: This pharmacovigilance study provides a systematic analysis of the clinical spectrum and reporting characteristics of ICI-related irAEs, comparing relative risks across vital organ systems and laying the foundation for interdisciplinary collaboration among oncologists and relevant specialists.