基于FAERS数据库的托珠单抗不良事件分析  

Tocilizumab related adverse events:A cross-section analysis of FDA Adverse Event Reporting System

作　　者：朱正怡[1] 倪映华[1] 高鹏[1] 王慧娟[1] 黄凌斐[1] 胡燕 张莉雯[1] 杨巨飞[1] 方罗 ZHU Zhengyi;NI Yinghua;GAO Peng;WANG Huijuan;HUANG Lingfei;HU Yan;ZHANG Liwen;YANG Jufei;FANG Luo(Department of Pharmacy,the Children's Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,Hangzhou 310052,Zhejiang,China)

机构地区：[1]浙江大学医学院附属儿童医院药剂科,国家儿童健康与疾病临床医学研究中心,浙江杭州310052

出　　处：《中国临床药理学与治疗学》2020年第8期895-902,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：浙江大学新型冠状病毒肺炎(COVID-19)应急科研专项资金资助;浙江省151人才工程(方罗);浙江省医坛新秀培养工程(方罗)。

摘　　要：目的:利用FDA不良事件报告系统(FAERS)数据库分析托珠单抗不良事件(AE),为新型冠状病毒肺炎患者提供安全用药信息。方法:从FAERS数据库中提取托珠单抗相关AE报告,采用报告比值比法和综合标准法检测潜在AE信号。结果:2014年7月至2019年3月FAERS数据库中以托珠单抗为主要或次要怀疑药物的初次报告19773例,药物无效、疼痛、药物不耐受、疲劳、皮疹等最为常见。严重不良事件13642例,导致死亡602例。严重和导致死亡的AE报告占比男性显著高于女性,儿童和老年显著高于中青年。报告比值比法和综合标准法分别检出潜在信号602个和490个,包括感染、药物超敏反应、白细胞减少、肝酶升高等常见AE,以及肺纤维化、间质性肺疾病、胰腺毒性、脱髓鞘病变等说明书未提示的AE信号。结论:托珠单抗常见报告药物无效、疼痛、药物不耐受、疲劳、皮疹等。肺纤维化、间质性肺疾病、胰腺毒性、脱髓鞘病变等未被说明书提示,需在临床中关注验证。AIM:To analyze the adverse events(AE)of tocilizumab by using the FDA Adverse Event Reporting System(FAERS)database.METHODS:AE reports related to tocilizumab were extracted from the FAERS database.Disproportionality analysis of reporting odds ratio(ROR)and Medicines and Healthcare Products Regulatory Agency(MHRA)methods were performed for safety signal detection.RESULTS:A total of 19773 reports associated with tocilizumab as the primary or secondary suspected drugs were extracted from the FAERS database between July 2014 to March 2019.AEs of drug ineffective,pain,drug intolerance,fatigue and rash were commonly reported.There were 13642 serious AE reports,and 602 reports of death outcome.The proportion of serious and death outcome AEs of male patients was significantly higher than female,and these proportions were significantly higher in children and elderly compared with others.Respectively 602 and 490 of tocilizumab signals were detected by ROR method and MHRA method,including common AEs such as infection,drug hypersensitivity,leukopenia,and hepatic enzyme increased,and signals not indicated in label,for instance,pulmonary fibrosis,interstitial lung disease,pancreatic toxicity and demyelination,were also detected.CONCLUSION:The commonly reported AEs of tocilizumab include drug inefficiency,pain,drug intolerance,fatigue and rash.Pulmonary fibrosis,interstitial lung disease,pancreatic toxicity and demyelination,which not indicated in label,should be further assessed and be cautious in COVID-19 treatment.

关 键 词：托珠单抗 不良事件 FDA不良事件报告系统 信号检测 

分 类 号：R593.22[医药卫生—内科学] R979.5[医药卫生—临床医学]