Multidimensional Assessment of Neurological Adverse Reactions Related to PD ‐1 Inhibitors: A Real‐World Pharmacovigilance Study

BACKGROUND: PD-1 inhibitors have revolutionized cancer immunotherapy but present significant neurological safety concerns. While clinical trials have documented neurological adverse events (nAEs), a comprehensive understanding of their patterns and risk factors remains limited. This study systematically analyzed a decade of FAERS data to investigate PD-1 inhibitor-associated neurotoxicities. METHODS: Using FAERS data (2014-2024), we conducted disproportionality analyses (ROR, IC, PRR) to assess PD-1 inhibitor-nAE associations. Risk factors were evaluated using logistic regression; timing analyses used log-rank and Mann-Whitney U tests, while group comparisons used Chi-square tests. RESULTS: Among 115,000 PD-1 inhibitor-associated adverse events, 7968 (6.93%) involved nAEs, showing an increasing trend from 4.96% (Q4 2014) to 7.67% (Q1-Q2 2024). PD-1 inhibitors showed significant nAE signals (ROR: 1.21, 95% CI: 1.18-1.23), with cemiplimab showing the strongest association (ROR: 1.38, 95% CI: 1.18-1.62). The most common nAEs were dizziness (N = 942, 10.3%), encephalitis (N = 435, 4.8%), and cerebrovascular accident (N = 451, 4.9%). Risk factors included age > 65 years (OR: 1.10), female sex (OR: 1.04), skin cancer (OR: 1.36), and nervous system cancers (OR: 1.44). The median onset time was 34 days (IQR: 12-104), with 63.8% occurring within 2 months and 59% resulting in severe outcomes. CONCLUSION: This study reveals a spectrum of PD-1 inhibitor-related neurological toxicities, mainly involving central nervous system dysfunction, providing important insights into risk patterns and timing characteristics. These findings support improved clinical monitoring practices and inform the development of personalized patient care strategies.