| アブストラクト | INTRODUCTION: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but traditional pharmacovigilance lacks a translational computational framework capable of resolving target-specific nonlinear temporal risks of adverse events such as hypokalemia. METHODS: We integrated 3,243 ICI-related hypokalemia reports from the FDA Adverse Event Reporting System (FAERS) and VigiBase (2014-2024). An ensemble signal-detection strategy cross-validated four disproportionality algorithms (Reporting Odds Ratio [ROR], Proportional Reporting Ratio [PRR], Empirical Bayesian Geometric Mean [EBGM], and Information Component [IC]). Flexible nonlinear survival analysis was performed using restricted cubic spline (RCS) Cox regression to model time-to-event dynamics. RESULTS: Programmed Death-Ligand 1 (PD-L1) inhibitors triggered the strongest signal (ROR = 3.20, 95% CI: 2.95-3.48), with ultra-early onset (median 23 days) and the highest case fatality rate (23.7%). An asymmetric biphasic mortality pattern showed a nadir at 60 days: early-onset (</=30 days) hypokalemia peaked at a hazard ratio (HR) of approximately 1.9, whereas late-onset (>90 days) risk gradually rose to HR approximately 1.8 within 350 days. Programmed Death-1 (PD-1) inhibitors significantly increased severe hypokalemia risk (odds ratio [OR] = 28.32), with male predominance across PD-1 and CTLA-4 subgroups. DISCUSSION: This interpretable ensemble framework reveals target-specific temporal toxicity signatures from multi-source real-world data, providing a computationally grounded translational pharmacology foundation for precision electrolyte monitoring and mechanism-informed safety prediction. |
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| ジャーナル名 | Frontiers in pharmacology |
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| Pubmed追加日 | 2026/10/17 |
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| 投稿者 | Chen, Shengwang; Dai, Ziyi; Guo, Zihan; Li, Ziyi; Liu, Ruiqi; Jiang, Xuewen |
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| 組織名 | Department of Neurosurgery, The Third Hospital of Xiamen, Xiamen City, Fujian,;China.;The Second Clinical College of China Medical University, Shenyang, China.;Dalian Medical University, Dalian, China.;The First Clinical College of China Medical University, Shenyang, China.;Department of Neurosurgery, Xiamen Xinglin Hospital, Xiamen, China. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/42889006/ |
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