基于FDA药品不良事件报告系统对托珠单抗不良事件信号的挖掘与分析

Data-mining and analysis of adverse drug events signals of tocilizumab based on FDA adverse event reporting system

目的通过对美国FDA药品不良事件自发呈报系统(FAERS)2015-2020数据库中有关托珠单抗上市后不良事件进行分析,为临床用药监测及不良事件应对提供参考。方法FDA官网下载2015年第1季度至2020年第2季度共22个季度的数据,用My Sql和Med Ex进行数据提取、规整和标准化,Med DRA进行不良事件术语汉化,用报告比值比法(ROR)和比例报告比值法(PRR)进行信号检测。结果经过数据规整和标准化后,共得到不良事件报告6459203例,其中以托珠单抗或包含托珠单抗为首要怀疑药品的报告22100例。在该22100例中,性别未知/空值1735例,男女比例为0.247;上报人职业以消费者为主;患者已知年龄分组中以成人为主;不良事件转归中以“其他严重的医疗事件”占比最高;用药原因中排名前三的分别是类风湿性关节炎、药品使用的适应证不明和幼年特发性关节炎;报告例数前20位的不良事件中只有6种没有检测出信号。该研究所使用的季度数据中报告例数最高的不良事件是药物无效,且ROR法检测出信号,而与COVID-19患者治疗相关的报告共93份,不良事件多为超说明书用药、故意使用导致的产品问题、血压波动、肝功能损害等,结果较严重。结论综合信号检出结果和文献资料,建议临床在给患者使用托珠单抗时,需考虑到药物相互作用,定期监测患者生化指标和白介素-6的水平,做好应对药物不良事件的准备。

AIM To provide reference for clinical drug monitoring and adverse events response by analyzing adverse events related to tocilizumab based on FDA adverse event reporting system(FAERS)2015-2020 database.METHODS The data of 22 quarters from the first quarter of 2015 to the second quarter of 2020 were downloaded from FDA website.My Sql and MedEx were used for data extraction,regularization and standardization.MedDRA was used to translate the terms of adverse event into Chinese.Reporting odds ratio(ROR)and proportional reporting ratio(PRR)were used for signal detection.RESULTS After data regularization and standardization,a total of 6459203 cases of adverse event reports were obtained,including 22100 cases of suspected drugs with or containing tocilizumab.Among 22100 cases,the gender of 1735 cases were unknown or null value,with a male to female ratio of 0.247.The reporter’s occupation was mainly consumer,the majority of patients in the known age group were adults,and“other serious medical events”accounted for the highest proportion of adverse events.The top three reasons of drug use were rheumatoid arthritis,unknown indications for drug use and juvenile idiopathic arthritis.Only 6 of the top 20 cases reported had no signal.In the quarterly data used in this study,the highest number of reported adverse events was drug ineffective,and the signal was detected by ROR method.There were 93 reports related to the treatment of patients with COVID-19,most of the adverse events were off label use,intentional product use issue,blood pressure fluctuation,and hepatic impairment,etc.and the results of adverse events were serious.CONCLUSION Based on the signal detection results and literature,it is suggested that the drug interaction should be taken into account when the patients are given tocilizumab,and the biochemical indexes and IL-6 levels of patients should be regularly monitored to prepare for adverse drug events.