肿瘤免疫治疗药物程序性死亡分子/程序性死亡配体抑制剂的不良反应挖掘及评价  

Adverse reactions of tumor immunotherapy drugs-PD-1/PD-L1 inhibitors

作　　者：陈爽 郑淑芬 张述耀 钟诗龙 CHEN Shuang;ZHENG Shufen;ZHANG Shuyao;ZHONG Shilong(Department of Pharmacology,Shantou University Medical College,Shantou Guangdong 515000,China;Department of Pharmacy,Guangdong Provincial People’s Hospital,Guangdong Academy of Medical Sciences,Guangzhou Guangdong 510080,China;Department of Pharmacy,Guangzhou Red Cross Hospital,Jinan University,Guangzhou Guangdong 510000,China;School of Pharmaceutical Sciences,Southern Medical University,Guangzhou Guangdong 510515,China)

机构地区：[1]汕头大学医学院药理学教研室,广东汕头515000 [2]广东省人民医院药学部,广东省医学科学院,广东广州510080 [3]暨南大学附属广州红十字会医院药学部,广东广州510000 [4]南方医科大学药学院,广东广州510515

出　　处：《中国药物警戒》2022年第10期1107-1112,共6页Chinese Journal of Pharmacovigilance

基　　金：2020年广东省科技专项资金项目[汕府科(2020)53号-20200602]。

摘　　要：目的横向比对4种国内上市的进口免疫检查点抑制剂(ICI)—PD-1/PD-L1抑制剂药品不良反应(ADR),并纵向比对其上市前后ADR,为临床合理安全使用ICI提供参考。方法通过美国食品药品监督管理局(FDA)不良事件报告系统(FAERS)和OpenVigil平台对2013年1月21日至2020年9月30日的PD-1/PD-L1抑制剂ADR上报数据清洗与汇总,通过报告比值比(ROR)法进行ADR信号的筛选、统计和比对。结果共获得44220份ADR(纳武利尤单抗27773份,帕博利珠单抗12424份,阿特珠单抗2875份,度伐利尤单抗1148份)。根据系统-器官分类法(SOC),ADR信号涉及的覆盖范围较大。ADR多为免疫相关不良反应(irAE),常见为结肠炎、肺炎、肝功能异常和内分泌疾病的甲亢和Ⅰ型糖尿病;深层次挖掘出说明书未提及的其他ADR,包括胆管炎、肌炎、心肌炎、关节炎、神经疾病(如脑梗死)、脑水肿等。结论进一步完善了PD-1/PD-L1抑制剂ADR信息,其ADR多为irAE,涉及全身多个系统-器官,严重时易危及患者生命。建议临床优化用药方案,减少患者治疗成本和ADR的发生。Objective To provide data for rational and safe use of ICI in clinical practice via a comparison of the adverse drug reactions(ADR)caused by four types of PD-1/PD-L1 inhibitors,whose imported immune checkpoint inhibitors(ICI)are marketed in China.Methods The data on PD-1/PD-L1 inhibitors collected between January 21,2013 and September 30,2020 was cleaned and summarized by the FDA Adverse Event Reporting System(FAERS)and OpenVigil platform.Signals of ADR were screened,counted and compared using the report odds ratio(ROR).Results A total of 44220 ADR cases were reported(27773 cases related to nivolumab,12424 cases to pembrolizumab,2875 cases to atezolizumab,and 1148 cases to durvalumab).The ADR covered a wide range according to the system organ classification(SOC).Most of those ADR were immune-related adverse events(irAE),such as colitis,pneumonia,liver dysfunction,hyperthyroidism and type I diabetes.Deeper mining exposed other ADR that were not mentioned in the instructions,including cholangitis,muscle Inflammation,myocarditis,arthritis,neurological diseases(such as cerebral infarction),and cerebral edema.Conclusion The information about ADR of PD-1/PD-L1 has been updated.Most of these ADR are irAE,involving multiple organs and systems of the body,which could be fatal in some cases.It is recommended that medication regimens be optimized to reduce the health care cost and ADR.

关 键 词：PD-1/PD-L1抑制剂 药品不良反应 免疫治疗 免疫相关不良反应 

分 类 号：R994.1[医药卫生—毒理学]