基于FAERS对3种JAK抑制剂相关主要心血管不良事件及恶性肿瘤不良事件的真实世界研究  

Real-world study of major cardiovascular adverse events and malignancy adverse events associated with 3 JAK inhibitors based on FAERS

作　　者：舒家华 李国兴 向秋林 陈松[1,2] 余娴 SHU Jia-hua;LI Guo-xing;XIANG Qiu-lin;CHEN Song;YU Xian(Department of Phase I Clinical Trial Center,The Second Affiliated Hospital of Chongqing Medical University,Chongqing 400010;College of Pharmacy,Chongqing Medical University,Chongqing 400016)

机构地区：[1]重庆医科大学附属第二医院Ⅰ期临床试验中心,重庆400010 [2]重庆医科大学药学院,重庆400016

出　　处：《中南药学》2023年第7期1966-1972,共7页Central South Pharmacy

基　　金：国家自然科学基金资助项目(No.82072327);重庆医科大学附属第二医院“宽仁英才”项目基金(No.kryc-gg-2209)。

摘　　要：目的挖掘和评价Janus激酶(JAK)抑制剂的主要心血管不良事件(MACE)、恶性肿瘤有关的具体药物不良事件(ADE)信号,为临床合理用药提供参考。方法提取美国食品药品管理局不良事件报告系统数据库中3种JAK抑制剂(托法替尼、巴瑞替尼、乌帕替尼)从上市以来至2022年第一季度的MACE和恶性肿瘤有关的ADE数据,使用医学活动监管词典(Med DRA)的标准Med DRA查询确定首选术语(PT),并采用英国药品和保健品管理局的综合标准法及报告比值比法对心血管、恶性肿瘤ADE进行信号挖掘。结果共检测出与托法替尼、巴瑞替尼和乌帕替尼目标ADE有关的阳性信号148例、128例和200例。女性发病人数均多于男性,多发于18~65岁年龄段,结局主要以住院或住院时间延长为主。3种JAK抑制剂共检测出51种PT信号,托法替尼、巴瑞替尼和乌帕替尼的目标PT分别检出18种、20种和20种。信号分析显示,在MACE方面,托法替尼可能与增加患者发生肥厚性心脏病的风险存在关联;巴瑞替尼的剂量与目标患者的MACE发生率成正相关;乌帕替尼暂不能确定与MACE存在关联。在恶性肿瘤方面,暂不能确定所报告的与恶性肿瘤有关的ADE与3种JAK抑制剂存在关联。结论基于3种JAK抑制剂在真实世界不良事件的研究,提示临床医务人员在使用时应注意观察该类药物可能的与MACE和恶性肿瘤相关的药物不良反应。Objective To mine and evaluate Janus kinase(JAK)inhibitors with major adverse cardiovascular events(MACE)and malignancy-related adverse drug events(ADE)signals to provide a reference for rational clinical use.Methods The MACE and malignancy-related ADE data of the 3 JAK inhibitors(tofacitinib,baricitinib,and upadacitinib)from the U.S.Food Drug Administration adverse event reporting system database since their launch until the first quarter of 2022 were collected with the Medical Dictionary for Regulatory Activities(Med DRA)'s standardized Med DRA query(SMQ)to identify preferred terms(PT).The UK Medicines and Healthcare Products Regulatory Agency's combined standard method and reporting ratio method were used for cardiovascular and malignancy ADEs for signal detection.Results Totally 148 cases,128 cases and 200 cases of positive signals related to target ADE of tofacitinib,baricitinib and upadacitinib were detected.Women had higher incidences than men,mostly in the 18~65 year old,and the outcomes were mainly hospitalization or prolonged hospitalization.Totally 51 PT were detected for the 3 JAK inhibitors;18,20 and 20 target PT were detected for tofacitinib,baricitinib and upadacitinib,respectively.Signal analysis showed that in terms of MACE,tofacitinib might be associated with an increased risk of hypertrophic heart disease in patients;the dose of baricitinib was positively correlated with the incidence of MACE in target patients;and no association with MACE was established at this time for upadacitinib.For malignancy,the association between the reported ADEs associated with malignancy and the 3 JAK inhibitors was not determined at this time.Conclusion Based on study of real-world adverse events with the 3 JAK inhibitors,clinical staff should be aware of the possible MACE-and malignancy-related adverse drug reactions associated with these drugs.

关 键 词：JAK抑制剂 主要心血管不良事件 恶性肿瘤不良事件 信号挖掘 

分 类 号：R994.1[医药卫生—毒理学]