与免疫检查点抑制剂相关的肝胆不良事件:使用FAERS数据进行现实世界药监分析
Yuzhu Chen1,2, Yixin Zeng1, Kaisheng Zhang3
1Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
Thoracic cancer
|November 17, 2025
概括
免疫检查点抑制剂 (ICI) 可以导致肝损伤. PD-L1 抑制剂与严重的肝病有关,而PD-1 抑制剂与肝炎有关,因此需要针对特定药物进行监测,以获得更安全的癌症治疗.
科学领域:
- 在瘤学瘤学.
- 肝病学 肝病学是一种肝病学.
- 药物监督 药物监督 药物监督
背景情况:
- 免疫检查点抑制剂 (ICI) 是重要的癌症疗法,但具有显著肝胆毒性的风险.
- 之前对ICI诱导的肝损伤的研究受限于小样本大小和病例报告.
- 了解特定的毒性概况和时间趋势对于安全的ICI管理至关重要.
研究的目的:
- 用大型不良事件数据库评估和比较与不同ICI相关的肝胆毒性.
- 为了确定PD-1和PD-L1抑制剂中毒性风险和时间模式的变化.
- 为更安全的ICI临床使用提供基于证据的指导.
主要方法:
- 分析了超过1860万的FDA不良事件报告系统 (FAERS) 报告,从2004年到2024年.
- 不成比例性分析 (ROR,PRR,EBGM,BCPNN) 以检测肝胆毒性的安全信号.
- 对AE发病时间和对人口风险因素的后勤回归的韦布尔建模.
主要成果:
- PD-L1抑制剂 (杜尔瓦卢马布,阿特索利祖马布) 与免疫媒介性肝病和肝功能衰竭的相关性更强 (ROR 4.28-5.07).
- PD-1 抑制剂 (Nivolumab,Pembrolizumab) 更频繁地与肝炎和肝脏异常有关 (ROR 3.42-3.93).
- 平均AE发病时间有所不同:托里帕利马布肝损伤23天,而提斯莱利祖马布自身免疫性肝炎84天.
结论:
- PD-L1 抑制剂与严重的免疫媒介性肝损伤和肝衰竭更强烈地相关.
- PD-1 抑制剂更常见地与肝炎和一般肝脏异常有关.
- 药物特异性监测,特别是在治疗的前三个月内,对于管理ICI相关的肝毒性至关重要.
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