摘要
目的基于美国食品药品监督管理局不良事件报告系统(FAERS)数据库挖掘细胞程序性死亡1受体(PD-1)/细胞程序性死亡-配体1(PD-L1)抑制剂的肝脏相关药物不良事件(ADE)风险信号,为临床安全用药提供参考。方法提取FAERS数据库中以帕博利珠单抗、纳武利尤单抗、阿替利珠单抗、度伐利尤单抗为首要怀疑药物的肝脏相关ADE报告,利用报告比值比(ROR)法进行数据挖掘,根据《国际医学用语词典》(27.0版)ADE术语集中的首选术语(PT)对ADE信号进行描述。结果共获得肝脏相关ADE报告14898份,其中帕博利珠单抗5349份,纳武利尤单抗6320份,阿替利珠单抗2440份,度伐利尤单抗789份。4种PD-1/PD-L1抑制剂肝脏相关ADE报告都以男性为主,患者年龄集中于65~85岁,ADE类型都以严重ADE为主,上报国家都以日本为主。经ROR法筛选后最终获得纳武利尤单抗相关ADE信号19个,阿替利珠单抗18个,帕博利珠单抗16个,度伐利尤单抗7个。其中,度伐利尤单抗与药物性肝损伤关联性最强,阿替利珠单抗与肝炎、肝脏疾病及肝功能异常关联性最强,帕博利珠单抗与肝细胞溶解、免疫介导性肝脏疾病关联性最强,纳武利尤单抗与免疫介导性肝炎关联性最强。肝细胞溶解、肝坏死、肝出血、肝破裂、肝萎缩、肝肾综合征等PT未被药品说明书收录。结论不同PD-1/PD-L1抑制剂肝脏相关ADE风险有所差异。临床应加强对PD-1/PD-L1抑制剂所致肝毒性的认识,重点关注药品说明书中未提及且易导致不良后果的ADE。使用PD-1/PD-L1抑制剂前应做好患者的用药评估,尤其是伴有肝功能损伤的患者。
Objective To mine risk signals for liver adverse drug events(ADE)related to programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1)inhibitors based on the American Food and Drug Administration Adverse Event Reporting System(FAERS)so as to provide evidence for safe clinical medication.Methods The liver ADE reports from the FAERS database with pembrolizumab,nivolumab,atezolizumab and durvalumab as the primary suspected drugs were extracted,and the reporting odds ratio(ROR)method was used for data mining.ADE signals were described according to the preferred term(PT)in Medical Dictionary for Regulatory Activities(27.0 edition).Results A total of 14898 liver related ADE reports were obtained,including 5349 cases of pembrolizumab,6320 cases of nivolumab,2440 cases of atezolizumab,and 789 cases of durvalumab.The liver ADE reports related to the four PD-1/PD-L1 inhibitors mainly occurred in male;patients aged between 65 and 85 years old;the severe ADE was the main type;and Japan was the main reporting country.After screened by the ROR method,19,18,16,and 7 ADE signals related to nivolumab,atezolizumab,pembrolizumab,and durvalumab were obtained,respectively.Among them,durvalumab had the greatest association with drug-induced liver injury,atezolizumab had the greatest association with hepatitis,liver disorder,and hepatic function abnormalities,pembrolizumab had the greatest association with hepatic cytolysis and immune-mediated hepatic disorder,and nivolumab had the greatest association with immune-mediated hepatitis.PT such as hepatic cytolysis,hepatic necrosis,hepatic haemorrhage,hepatic rupture,hepatic atrophy,and hepatorenal syndrome were not recorded in drug instructions.Conclusion The risk for liver ADEs vary among different PD-1/PD-L1 inhibitors.Clinical efforts should strengthen the understanding of liver toxicity caused by PD-1/PD-L1 inhibitors,with a focus on ADE that is not mentioned in drug instructions and is prone to adverse consequences.Before using PD-1/PD-L1 inhibitors,patient medication evaluation should be done,especially for patients with abnormal liver function.
作者
狄潘潘
邢晓勤
梁海
贾淑云
DI Panpan;XING Xiaoqin;LIANG Hai;JIA Shuyun(Department of Pharmacy,the Affiliated Bozhou Hospital of Anhui Medical University(the People's Hospital of Bozhou),Bozhou 236800,China)
出处
《浙江医学》
2025年第5期517-523,共7页
Zhejiang Medical Journal
基金
安徽医科大学校基金资助项目(2023xkj091)
亳州市人民医院院级科研项目(by2023006)。
