Immune checkpoint inhibitor-associated aseptic meningitis: a pharmacovigilance study using the FDA adverse event reporting system (2011-2024).

Objective: Immune checkpoint inhibitors (ICIs) are pivotal in oncology but carry risks of immune-related adverse events (irAEs). Aseptic meningitis (AM) represents a serious neurological irAE, yet real-world evidence on regimen-specific risk variations remains limited. This study aimed to characterize AM reporting patterns and safety signals across ICI regimens using FDA Adverse Event Reporting System (FAERS) data. Methods: We analyzed FAERS reports (January 2011-December 2024) for ICIs-associated AM. Descriptive statistics summarized demographics, clinical profiles, and temporal trends. Disproportionality analyses employed four algorithms: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Results: Among 498 ICIs-associated AM reports, monotherapy predominated (78.7%) with pembrolizumab (34.9%), ipilimumab/nivolumab (21.3%), nivolumab (17.1%), and atezolizumab (15.9%) as leading agents. Patients had a median age of 64 years; 98% met serious adverse event criteria. Hospitalization (45.8%) was the most common outcome. Symptom onset was rapid (median: 34 days). Disproportionality analysis revealed pronounced signals for ipilimumab/nivolumab (ROR 5.71, 95% CI 4.71-6.91) and ipilimumab monotherapy (ROR 4.21, 95% CI 3.05-5.82). Anti-PD-1 agents collectively showed moderate association (ROR 2.55, 95% CI 2.25-2.88). Conclusions: ICIs-associated AM presents a clinically significant safety concern, particularly with ipilimumab-containing regimens. Rapid symptom onset underscores the need for vigilant neurological monitoring during early treatment phases. These findings warrant integration into clinical risk-assessment protocols and warrant further mechanistic investigation.