Immune checkpoint inhibitor-associated autoimmune encephalitis and other neurological immune-mediated adverse events: a pharmacovigilance study using the FAERS and JADER

Immune checkpoint inhibitor (ICI)-associated neurological immune-related adverse events (NAEs) are rare but serious side effects, of which autoimmune encephalitis (AIE) is a potentially fatal central nervous system disorder requiring more attention. We performed a retrospective disproportionality an...

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Published in:Frontiers in oncology Vol. 15; p. 1621045
Main Authors: Di, Xiaomeng, Shi, Xiaohong, Gai, Feng, Wang, Jiawei
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 17.07.2025
Subjects:
autoimmune encephalitis
FAERS
immune checkpoint inhibitor
immune-related adverse events
Oncology
pharmacovigilance
autoimmune encephalitis
FAERS
immune checkpoint inhibitor
pharmacovigilance
immune-related adverse events
ISSN:2234-943X, 2234-943X
Online Access:Get full text
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Summary:Immune checkpoint inhibitor (ICI)-associated neurological immune-related adverse events (NAEs) are rare but serious side effects, of which autoimmune encephalitis (AIE) is a potentially fatal central nervous system disorder requiring more attention. We performed a retrospective disproportionality analysis of NAE reports in the FDA Adverse Event Reporting System (FAERS) and the Japanese Adverse Event Reporting Database (JADER) from 2004 to 2024, utilizing reporting odds ratio (ROR), proportional reporting ratio (PRR), the Bayesian confidence propagation neural network BCPNN, and the multi-item gamma Poisson shrinker (MGPS) for signal detection. In total, 3,999 reports of ICI-associated NAEs were identified from the FAERS database, of which 1,998 reports were AIE. 1,558,251 reports of AEs were collected from the JADER database, which contained 890 AIE reports. ICIs, including pembrolizumab, nivolumab, atezolizumab, ipilimumab, and durvalumab, were identified among the top 30 agents in both databases, demonstrating significant signals across all 4 algorithms. Except for noninfectious myelitis, acute disseminated encephalomyelitis, and multiple sclerosis, positive signals were detected in all other preferred terms (PTs). These NAEs accounted for 23.7% of total mortality, with myasthenia gravis (MG) exhibiting the highest mortality rate at 30.63%. Specific PTs, such as aseptic meningitis, AIE, chronic inflammatory demyelinating polyradiculoneuropathy, Guillain-Barré syndrome, MG, myelitis, and immune-related myopathy, were associated with the severity of outcomes, showing significant statistical differences between severe and non-severe cases (p < 0.05). Our study found a notable correlation between ICIs and AIE and other specific NAEs, highlighting the demographic characteristics, time to onset, and disease severity of ICI-induced NAEs, thereby facilitating the timely recognition and treatment of these ICI therapy-related complications.
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Edited by: Zhida Liu, Shanxi Academy of Advanced Research and Innovation, China
Reviewed by: Tongyi Huang, The First Affiliated Hospital of Sun Yat-sen University, China
These authors have contributed equally to this work and share first authorship
Songyan Han, Shanxi Cancer Hospital Urology Surgery, China
ISSN:2234-943X
2234-943X
DOI:10.3389/fonc.2025.1621045