基于美国FDA不良事件报告系统数据库的阿替利珠单抗风险信号分析  

Analysis on the risk signal mining related to atezolizumab based on the United States Food and Drug Administration Adverse Event Reporting System

作　　者：孔庆丽[1] 彭净[2] 王芳[3] 杜芹[3] 冯蕾[2] 任晓蕾 王美霞[1] KONG Qingli;PENG Jing;WANG Fang;DU Qin;FENG Lei;REN Xiaolei;WANG Meixia(PhaseⅠClinical Trial Laboratory,Affiliated Hospital of Jining Medical University,Jining 272029,China;Department of Pharmacy,Affiliated Hospital of Jining Medical University,Jining 272029,China;Department of Oncology,Affiliated Hospital of Jining Medical University,Jining 272029,China;Medical Big Data Center,Affiliated Hospital of Jining Medical University,Jining 272029,China)

机构地区：[1]济宁医学院附属医院Ⅰ期临床试验研究室,济宁272029 [2]济宁医学院附属医院药学部,济宁272029 [3]济宁医学院附属医院肿瘤科,济宁272029 [4]济宁医学院附属医院医学大数据中心,济宁272029

出　　处：《中国临床药学杂志》2023年第1期34-41,共8页Chinese Journal of Clinical Pharmacy

基　　金：济宁市重点研发计划项目(政策引导类)(编号2022YXNS067);山东省药学会医院合理用药天际健康中青年科研学术活动课题(编号hlyy2021-03)。

摘　　要：目的了解阿替利珠单抗的主要不良事件(AE)及其发生风险,为该药临床安全应用提供参考。方法收集美国FDA不良事件报告系统数据库2016年第2季度至2021年第4季度收录的阿替利珠单抗AE报告,采用比例报告比值比(PRR)法进行AE风险信号挖掘。AE报告数≥3、PRR≥2且χ^(2)≥4的AE被定义为阳性风险信号。采用国际医学用语词典(MedDRA)v24.0的首选系统器官分类(SOC)和首选术语(PT)对AE进行分类统计,选取AE报告数和信号强度排名前50位的PT进行分析。结果共收集到以阿替利珠单抗为首要怀疑药物的AE报告20311例,涉及PT 1484个,筛选出阳性风险信号402个。经第2次筛选,获得AE报告数排名前50位和PRR值排名前50位的PT,筛重后纳入分析的PT为98个,涉及AE报告9119例。AE报告数居前5位的PT为死亡(7.8%,715/9119)、发热(6.0%,546/9119)、肺炎(4.0%,363/9119)、腹泻(3.6%,331/9119)和粒细胞减少性发热(3.3%,300/9119);信号强度居前5位的PT为全身免疫激活(PRR=2413.39)、黄斑增厚(PRR=742.58)、内分泌毒性(PRR=412.55)、免疫介导性脑炎(PRR=386.14)、肿瘤成腔区形成(PRR=247.53)。涉及AE报告数居前5位的SOC依次为呼吸系统、胸及纵膈系统疾病(15.7%,1436/9119)、全身性疾病及给药部位各种反应(15.1%,1382/9119)、血液淋巴系统疾病(10.5%,961/9119)、胃肠系统疾病(8.7%,797/9119)和各类检查(8.7%,791/9119)。新发现的黄斑增厚、肿瘤成腔区形成等12个PT在药品说明书中未曾报告。结论阿替利珠单抗报告数较多的AE为死亡和发热、全身免疫激活和眼部疾病信号较强;新发现的黄斑增厚、肿瘤成腔区形成等12个PT对于指导临床合理用药具有重要意义。AIM To understand the main adverse events(AEs)and their risk of occurrence related to atezolizumab and provide reference for the safe use of the drug in clinic.METHODS The adverse event reports on atezolizumab included in the US Food and Drug Administration(FDA)Adverse Event Reporting System from the second quarter of 2016 to the forth quarter of 2021 were collected,and the AE risk signals were explored using proportional reporting odds ratio(PRR)method.AEs with≥3 reports,PRR value≥2,and χ^(2)≥4 were defined as positive risk signals.AEs were counted and classified using the preferred system organ class(SOC)and preferred term(PT)of Medical Dictionary for Regulatory Activities v24.0.The PTs of top 50 adverse event reports and signal intensity were selected and analyzed.RESULTS A total of 20311 adverse event reports with atezolizumab as the primary suspected drug were collected,involving 1484 PTs,and 402 positive risk signals were selected.After the second screening,the top 50 PTs in the number of adverse event reports and the top 50 PTs with great PRR values were obtained,and 98 PTs were included in the analysis after sifting out the repeated,involving 9119 adverse event reports.The top 5 PTs in the number of adverse event reports were death(7.8%,715/9119),pyrexia(6.0%,546/9119),pneumonia(4.0%,363/9119),diarrhoea(3.6%,331/9119),and febrile neutropenia(3.3%,300/9119).The top 5 PTs with the high signal intensity were systemic immune activation(PRR=2413.39),macular thickening(PRR=742.58),endocrine toxicity(PRR=412.55),immune-mediated encephalitis(PRR=386.14),and tumour cavitation(PRR=247.53).The top 5 SOC involving adverse event reports were respiratory,thoracic and mediastinal disorders(15.7%,1436/9119),general disorders and administration site conditions(15.1%,1382/9119),blood and lymphatic system disorders(10.5%,961/9119),gastrointestinal disorders(8.7%,797/9119),and various examinations(8.7%,791/9119).Twelve PTs were not included in the drug instructions,such as macular thickening and tumour cavitation,etc.

关 键 词：程序性死亡配体1 恶性肿瘤 药物不良反应报告系统 美国食品和药物管理局 信号处理 阿替利珠单抗 

分 类 号：R95[医药卫生—药学]