基于美国FDA不良事件报告系统数据库的GD2单抗不良事件风险信号挖掘  

Adverse event risk signal mining of anti‑disialoganglioside 2 monoclonal antibody based on US FDA Adverse Event Reporting System

作　　者：邵苗苗 孙熙木 周涵 李英[1] 孙一鑫 杨长青 王晓玲[1] 赵文[3] Shao Miaomiao;Sun Ximu;Zhou Han;Li Ying;Sun Yixin;Yang Changqing;Wang Xiaoling;ZhaoWen(Department of Pharmacy,Beijing Children′s Hospital,Capital Medical University,Beijing 100045,China;School of Basic Medicine and Clinical Pharmacy,China Pharmaceutical University,Nanjing 210008,China;Department of Medical Oncology,Beijing Children′s Hospital,Capital Medical University,Beijing 100045,China)

机构地区：[1]首都医科大学附属北京儿童医院药学部,北京100045 [2]中国药科大学基础医学与临床药学学院,南京210008 [3]首都医科大学附属北京儿童医院肿瘤内科,北京100045

出　　处：《药物不良反应杂志》2023年第10期592-600,共9页Adverse Drug Reactions Journal

基　　金：白求恩·求索-药学科研能力建设项目(Z04JKM2021005);医院药物警戒研究协作组医院药学科研专项(DRM2022013)。

摘　　要：目的了解达妥昔单抗、达妥昔单抗β和那西妥单抗3种双唾液酸神经节苷脂(GD2)单克隆抗体(单抗)的不良事件(AE)风险信号,为临床安全用药提供参考。方法收集美国FDA不良事件报告系统(FAERS)数据库中2015年至2023年第2季度以达妥昔单抗、达妥昔单抗β和那西妥单抗为首要怀疑和次要怀疑药物的AE报告。根据《国际医学用语词典》25.0版中的首选术语(PT)和系统器官分类(SOC)对AE进行标准化和分类,采用报告比值比(ROR)法和信息成分(IC)法进行AE风险信号挖掘。对3种GD2单抗的AE报告信息和AE风险信号进行描述性分析。结果共收集到以3种GD2单抗为首要怀疑和次要怀疑药物的AE报告630例,包括达妥昔单抗465例、达妥昔单抗β61例和那西妥单抗104例,涉及PT为341、24和125种,分别映射在19、2和12个SOC中。3种GD2单抗相关AE中,均有出现死亡、威胁生命、住院或住院时间延长不良结局的患者。采用ROR法和IC法进行信号挖掘,共检测出AE风险信号142、3和30个,其中未在相应药品说明书中记录的分别为73、0和6个。报告数居首位的PT,达妥昔单抗和达妥昔单抗β均为发热,那西妥单抗为低血压和疼痛;信号强度居首位的PT,达妥昔单抗、达妥昔单抗β和那西妥单抗分别为穿刺部位脓肿、器械相关的菌血症和喘鸣。3种药物重叠的AE风险信号为发热和疼痛,达妥昔单抗发热信号强度最强,那西妥单抗疼痛信号强度最强。在AE报告数前30位的PT中,那西妥单抗在呼吸系统、胸及纵隔疾病,皮肤及皮下组织类疾病,免疫系统疾病,血管与淋巴管类疾病的AE风险信号明显多于达妥昔单抗。那西妥单抗AE风险信号中,不同于达妥昔单抗且未在说明书中记录的PT为呼吸异常、发绀和代谢性酸中毒。结论发热、疼痛和低血压为3种GD2单抗常见AE。那西妥单抗引起疼痛明显,呼吸异常、发绀和代谢性酸中毒为该药独有且�Objective To understand the adverse event(AE)risk signals of 3 anti‑disialoganglioside 2(GD2)monoclonal antibodies,including dinutuximab,dinutuximab beta,and naxitamab,and to provide reference to clinical use.Methods AE reports with dinutuximab,dinutuximab beta,and naxitamab as the primary and secondary suspect drug were collected from the US FDA Adverse Event Reporting System(FAERS)database during 2015 to the 2nd quarter of 2023.AEs were standardized and classified according to the preferred term(PT)and system organ classification(SOC)in the International Medical Terminology Dictionary,Version 25.0,and AE risk signals were mined using the reporting odds ratio(ROR)method and information component(IC)method.The AE reports information and AE risk signals of 3 GD2 monoclonal antibodies were descriptively analyzed.Results A total of 630 AE reports were collected,in which the 3 GD2 monoclonal antibodies were the primary and secondary suspect drugs,including 465 reports of dinutuximab,61 reports of dinutuximab beta,and 104 reports of naxitamab,which involved 341,24,and 125 PTs and mapped to 19,2,and 12 SOCs,respectively.The AEs of the 3 GD2 monoclonal antibodies were associated with the occurrence of death,life‑threatening,hospitalization,or prolonged hospitalization adverse outcomes.Signal mining using ROR and IC methods detected a total of 142,3,and 30 AE risk signals,of which 73,0,and 6 were not documented in the corresponding drug instructions,respectively.The top PTs in report number were fever for both dinutuximab and dinutuximab beta,and hypotension and pain for naxitamab;the top PTs in signal intensity were puncture site abscess,device related bacteraemia,and wheezing for dinutuximab,dinutuximab beta,and naxitamab,respectively.The overlapping AE risk signals for the 3 drugs were fever and pain,with dinutuximab having the strongest signal intensity for fever and naxitamab having the strongest signal intensity for pain.Among the top 30 PTs in report number,naxitamab had significantly more AE risk signals than

关 键 词：神经母细胞瘤 抗体 单克隆 药物毒性 不良事件风险信号 双唾液酸神经节苷脂 那西妥单抗 达妥昔单抗 

分 类 号：R979.1[医药卫生—药品]