Drug-induced Aseptic Meningitis: Pharmacovigilance Analysis of Japanese Adverse Event Reporting Database

Drug-induced aseptic meningitis (DIAM) is a rare but clinically important adverse event. We identified drugs potentially associated with aseptic meningitis using the Japanese Adverse Drug Event Report (JADER) database.

We conducted a disproportionality analysis of aseptic meningitis adverse events using JADER data from April 2004 to October 2024. Disproportionality signals for aseptic meningitis were detected using reporting odds ratios (RORs) with 95% confidence intervals. The Weibull distribution was analyzed to evaluate the time to onset of adverse events for drugs producing symptoms of aseptic meningitis.

Nineteen drugs were identified as associated with aseptic meningitis: nine vaccines, three immunoglobulin products, two nonsteroidal anti-inflammatory drugs, and two immune checkpoint inhibitors (nivolumab and ipilimumab), among others. The onset of DIAM temporally associated with the SARS-CoV-2 RNA vaccine was typically observed within a few days following vaccination, resembling the temporal pattern reported for conventional DIAM. In contrast, the DIAM onset after nivolumab and ipilimumab treatment was delayed, leading to the classification of these drugs as random failure types, which is consistent with the timing of the immune-related adverse events.

DIAM onset patterns differ among therapeutic classes, including immune checkpoint inhibitors and SARS-CoV-2 RNA vaccines. These differences in onset timing suggest that DIAM onset occurs through distinct pathophysiological mechanisms. This information may support differential diagnosis and guide management of aseptic meningitis in clinical settings.