摘要
目的探讨不同品种免疫检查点抑制剂(ICI)致胆管炎的风险。方法通过开放性OpenVigil数据平台,收集美国FDA不良事件报告系统(FAERS)数据库2011年第1季度至2021年第3季度纳武利尤单抗、帕博利珠单抗、西米普利单抗、阿维鲁单抗、度伐利尤单抗、阿替利珠单抗、伊匹木单抗和替西木单抗的药品不良事件(AE)报告,采用报告比值比(ROR)法进行胆管炎风险信号挖掘,风险信号的检测阈值设定为AE报告数≥3且ROR的95%置信区间(CI)下限>1。ROR及其95%CI下限值越大表示信号强度越大。比较不同品种ICI导致胆管炎的风险信号强度,并对ICI相关胆管炎患者的主要特点(性别、年龄、原发肿瘤类型、AE发生时间和结局等)进行描述性分析。结果收集到ICI相关AE报告52440例,其中胆管炎报告410例。检测出阳性风险信号的药物有纳武利尤单抗、帕博利珠单抗、阿替利珠单抗、度伐利尤单抗单药治疗和伊匹木单抗联合纳武利尤单抗,其AE报告数分别为213、107、48、5和29(共402例),ROR(95%CI下限)分别为37.88(32.89)、26.07(21.46)、32.12(24.10)、13.63(5.65)和14.46(10.02),风险信号强度为纳武利尤单抗>阿替利珠单抗>帕博利珠单抗>伊匹木单抗+纳武利尤单抗>度伐利尤单抗。有可用数据的报告中,男性多于女性(233例∶110例=2.1∶1),65岁及以上者占55.2%(222/402),非小细胞肺癌占48.0%(193/402)。ICI相关胆管炎可导致42.3%(170/402)的患者住院或住院时间延长,40.0%(161/402)需要紧急治疗,2.0%(8/402)危及生命,15.7%(63/402)死亡。结论不同品种ICI致胆管炎风险不同,以纳武利尤单抗风险信号最强。胆管炎是ICI的严重AE,应引起临床关注。
Objective To explore the risk of cholangitis induced by different immune checkpoint inhibitors(ICIs).Methods Through the OpenVigil data platform,adverse event(AE)reports related to nivolumab,pembrolizumab,cemiplimab,avelumab,durvalumab,atezolizumab,ipilimumab,and tremelimumab from the first quarter of 2011 to the third quarter of 2021 in the US FDA Adverse Event Reporting System(FAERS)database were collected.Risk signal mining for cholangitis was performed using reported odds ratio(ROR)method.The detection threshold of the risk signal was set as that the number of AE reports was greater than or equal to 3 and the lower limit of the 95%confidence interval(CI)of the ROR was greater than 1.The higher the ROR and its 95%CI lower limit,the stronger the signal intensity.The intensity of the risk signal of cholangitis due to different ICIs was compared and the main characteristics(sex,age,type of primary tumor,time of occurrence of AE,and outcome)of patients with ICIsrelated cholangitis were analyzed descriptively.Results A total of 52440 AE reports related to the above 8 ICIs were collected,of which 410 cases were about cholangitis.The drugs that were detected with positive risk signals were nivolumab,pembrolizumab,atezolizumab,durvalumab monotherapy,and ipilimumab combined with nivolumab.Their number of AE reports were 213,107,48,5,and 29(402 patients in total),and the corresponding ROR(lower limit of 95%CI)were 37.88(32.89),26.07(21.46),32.12(24.10),13.63(5.65),and 14.46(10.02),respectively.The risk signal intensity was nivolumab,atezolizumab,pembrolizumab,ipilimumab combined with nivolumab,and durvalumab in order.Seeing from the available data among the reports,males were more than females(233∶110=2.1∶1),55.2%(222/402)of patients were 65 years old and over,and 48.0%(193/402)of patients were nonsmall cell lung cancer.ICIsrelated cholangitis could result in hospitalization or prolongation of hospitalization in 42.3%(170/402),requiring emergency treatment in 40.0%(161/402),lifethreatening in 2.0%(8/402),and death in 15.7%(63/402)of patients.Conclusions The risk of cholangitis induced by ICIs is different and the risk signal of nivolumab is the strongest.Cholangitis is a serious AE of ICI,which should attract clinical attention.
作者
赵艳艳
张会鲜
孟路华
冯建博
Zhao Yanyan;Zhang Huixian;Meng Luhua;Feng Jianbo(Department of Pharmacy,Affiliated Hospital of Jining Medical University,Shandong Province,Jining 272029,China;Department of Oncology,Affiliated Hospital of Jining Medical University,Shandong Province,Jining 272029,China)
出处
《药物不良反应杂志》
CSCD
2022年第8期424-428,共5页
Adverse Drug Reactions Journal
基金
济宁市重点研发计划(2021YXNS122)
济宁医学院附属医院博士科研基金项目(2018‑BS‑012)。
关键词
抗肿瘤药
免疫检查点抑制剂
胆管炎
药物相关副作用和不良反应
Antineoplastic agents
Immune checkpoint inhibitors
Cholangitis
Drug‑related side effects and adverse reactions
