ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1654301
This article is part of the Research TopicCancer Therapy Related Organ ToxicitiesView all 15 articles
Immune checkpoint inhibitor-associated aseptic meningitis: A pharmacovigilance study using the FDA adverse event reporting system (2011-2024)
Provisionally accepted
- 1Shanxi Cardiovascular Hospital, Taiyuan, China
- 2Shanxi Medical University, Taiyuan, China
- 3Second Hospital of Shanxi Medical University, Taiyuan, China
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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.
Keywords: Immune Checkpoint Inhibitors1, aseptic meningitis2, Food and DrugAdministration's Adverse Event Reporting System3, pharmacovigilance4, datamining5
Received: 26 Jun 2025; Accepted: 22 Sep 2025.
Copyright: © 2025 Guo, Pang, Guo, Wang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Qian Guo, guoqian0402@gmail.com
Haixiong Wang, cz1976whx@126.com
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