目的 旨在利用FAERS数据库，评估接受帕博利珠单抗联合阿昔替尼的患者药品不良事件（ADE）信号及毒性风险。方法 提取2012年1季度—2024年3季度的FAERS数据，剔除重复报告后，利用比例失衡法和组合风险比模型挖掘两药联合使用ADE信号，并分析人群特征、毒性及重要医学事件（IME）和新信号。结果 共获取2 968例联合用药ADE报告，男性占比65.13%，女性占比27.53%;45～75岁年龄段患者占比59.37%；美国上报最多占比42.69%；联合用药的发病中位时间为60 d，较单药有所延长；频数较高的ADE主要为超说明书使用、腹泻、疲劳等；联合用药共有224例阳性信号，其中49个毒性信号、17个IME及50个新信号，主要涉及肝胆系统、肿瘤进展、胃肠系统疾病、各类神经系统疾病等。结论 帕博利珠单抗联合阿昔替尼治疗的ADE具有独特时间特征及新风险信号，临床需加强全程药学监护，重点关注高频事件及新信号相关系统毒性。

Objective This study aims to assess the drug adverse event signals and toxicity risks in patients receiving pembrolizumab combined with axitinib using the FDA Adverse Event Reporting System（FAERS） database. Methods Data from the FAERS database from the first quarter of 2012 to the third quarter of 2024 were extracted, and duplicate reports were removed. The disproportionality analysis and Combination Risk Ratio Model were used to mine adverse event signals. The demographic characteristics, toxicity, and important medical event（IME） signals and new signals of ADE were analyzed. Results A total of 2 968 ADE reports were obtained, including 65.13% of males and 27.53% of females. The age group of 45—74 years reported the most ADE of 59.37%. The United States reported the most cases of 42.69% people. The median onset time of combined medication was 60 d, which was longer than that of single medication. ADE with higher frequency are mainly super manual use, diarrhea, fatigue, etc. A total of 224 positive signals were identified in combination therapy, including 49 toxicity signals, 17 IME, and 50 new signals, mainly involving the liver and gallbladder system, tumor progression, gastrointestinal system diseases, various neurological diseases, etc. Conclusion ADE treated with pembrolizumab combined with axitinib have unique time characteristics, toxicity profiles and new risk signals. The clinical need to strengthen full-process pharmacological monitoring, focusing on high-frequency events and new signal-related toxicity.

R979.1

国家自然科学基金资助项目(82474375); 南京药学会-医院药学科研基金资助项目(2022YX022)