基于FAERS的免疫检查点抑制剂致高血糖风险分析  

Risk Analysis of Hyperglycemia Caused by Immune Checkpoint Inhibitors Based on FAERS

作　　者：谢波[1] 李志浩[1] XIE Bo;LI Zhihao(Sinopharm Dongfeng General Hospital Affiliated to Hubei University of Medicine,Shiyan,Hubei,China 442008)

机构地区：[1]湖北医药学院附属国药东风总医院,湖北十堰442008

出　　处：《中国药业》2024年第21期104-110,共7页China Pharmaceuticals

基　　金：湖北医药学院附属国药东风总医院卓越计划青年人才项目[2022Q32]。

摘　　要：目的为临床安全使用免疫检查点抑制剂(ICIs)提供参考。方法采用报告比值比(ROR)法及英国药品和保健品管理局(MHRA)综合标准法对美国食品和药物管理局不良事件报告系统(FAERS)中2017年第3季度至2022年第4季度接受5种ICIs(伊匹木单抗、纳武利尤单抗、帕博利珠单抗、阿替利珠单抗、度伐利尤单抗)治疗致高血糖的药品不良事件报告(ADE)进行信号挖掘。结果共收集到ICIs相关ADE报告271263份,ICIs相关高血糖ADE报告共3587份,涉及患者2927例。其中,男性占比高于女性(58.46%比34.51%);患者平均年龄为65.49岁,65岁及以上老年患者占比(48.21%)高于其他年龄段患者;5种ICIs均有死亡事件报告。ADE报告首选语中糖尿病的报告数最多(694份,19.85%),暴发性1型糖尿病[ROR=334.22,95%CI(270.69,412.66),PRR=333.71,χ2=28678.65]的信号最强;伊匹木单抗与高血糖症的相关性显著[ROR=158.24,95%CI(121.13,206.71),PRR=157.75,χ2=8401.64];1型糖尿病、暴发性1型糖尿病、糖尿病酮症酸中毒为5种ICIs共有的ADE阳性信号首选语。结论在肿瘤免疫治疗期间,ICIs可能导致高血糖,ICIs与1型糖尿病、暴发性1型糖尿病、糖尿病酮症酸中毒具有相关性。Objective To provide a reference for the safe use of immune checkpoint inhibitors(ICIs)in the clinic.Methods Signal mining was performed on adverse drug events(ADEs)reports of hyperglycemia caused by five ICIs(ipilimumab,nivolumab,pembrolizumab,atezolizumab,and dupixent)in the US Food and Drug Administration Adverse Event Reporting System(FAERS)from the third quarter of 2017 to the fourth quarter of 2022 by the reporting odds ratio(ROR)method and Medicines and Healthcare Products Regulatory Agency(MHRA)method.Results A total of 271263 ICIs-related ADE reports and 3587 ICIs-related hyperglycemia ADE reports were collected,involving 2927 patients.Among them,the proportion of males was higher than that of females(58.46%vs.34.51%);the average age of patients was 65.49 years old,and the proportion of elderly patients aged 65 and above(48.21%)was higher than that of patients in other age groups.All of the five ICIs reported fatality.In the preferred terms of ADE report,the number of reports of diabetes mellitus(DM)was the highest(694 cases,19.85%),and the signal of fulminant type 1 diabetes mellitus[ROR=334.22,95%CI(270.69,412.66),PRR=333.71,χ2=28678.65]was the strongest.There was a significant correlation between ipilimumab and hyperglycemia[ROR=158.24,95%CI(121.13,206.71),PRR=157.75,χ2=8401.64].Type 1 diabetes mellitus,fulminant type 1 diabetes mellitus,and diabetes ketoacidosis were the common preferred terms of five ICIs.Conclusion During tumor immunotherapy,ICIs may cause hyperglycemia.ICIs are associated with type 1 diabetes mellitus,fulminant type 1 diabetes mellitus,and diabetes ketoacidosis.

关 键 词：免疫检查点抑制剂 高血糖 美国食品和药物管理局不良事件报告系统 报告比值比法 英国药品和保健品管理局综合标准法 

分 类 号：R969.3[医药卫生—药理学] R979.1[医药卫生—药学]