乌帕替尼上市后不良反应评估:一项基于美国FDA不良事件报告系统数据库的真实世界研究

Evaluation of Adverse events of Upadacitinib:a Real-world Study Based on the US Food and Drug Administration Adverse Event Reporting System

目的:通过美国FDA不良事件报告系统(FDA Adverse Event Reporting System,FAERS)系统数据库,挖掘与分析乌帕替尼上市后药品不良事件(Adverse event,AE)信号,为其临床用药安全提供参考。方法:从FAERS数据库提取2019年第3季度至2023年第1季度的不良事件报告数据,采用报告比值比法(Reporting odds ratio,ROR)和比例报告比值法(Proportional reporting ratio,PRR)对乌帕替尼相关的不良事件报告进行信号挖掘与分析。结果:共提取了28743份以乌帕替尼为首要怀疑的不良事件报告,检测出315个阳性信号,涉及20个系统器官分类(System organ class,SOC)。阳性信号涉及SOC主要为“感染及侵染类疾病”、“各类损伤、中毒及操作并发症”、及“各种肌肉骨骼及结缔组织疾病”。报告频次前5位的信号的首选术语(Preferred terms,PT)为疼痛、COVID-19、肢体疼痛、肌肉骨骼强直、尿路感染。信号强度较高但说明书未记载的信号有握力减弱、腕管综合征、肌腱断裂、肌肉骨骼强直、白内障等。严重不良事件结果对应的PT主要为COVID-19、感染性肺炎心血管疾病、脑血管意外等。结论:临床使用乌帕替尼时,除需关注疼痛、感染等常见不良事件及说明书未提及的新不良事件外,还应重视严重感染、心脑血管意外、肺栓塞等严重不良事件结局检出的信号。

Objective:To explore the adverse event(AE)signals of upadacitinib in real-world by the US Food and Drug Administration Adverse Event Reporting System(FAERS)and improve the clinical safety of upadacitinib.Methods:The data from 2019Q3 to 2023Q1 adverse event reports in the FAERS were obtained.The reporting odds ratio(ROR)and proportional reporting ratio(PRR)were used to detect the risk signals of upadacitinib.Results:Totally 28743 AE reports which took the upadacitinib as the primary suspect(PS)drug were obtained from FAERs database,and 315 positive signals involving 20 system organ class(SOC)were detected.The positive signals most releted SOC were“infections and infestations”,“injury,poisoning and procedural complications”,“musculoskeletal and connective tissue disorders”.The top 5 frequently reported PTs were pain,COVID-19,pneumonia,pain in extremity,urinary tract infection.Some new signals with high ROR were found included grip strength decreased,carpal tunnel syndrome,tendon rupture,musculoskeletal stiffness,cataract.The serious outcomes main related PTs were COVID-19,pneumonia,cardiovascular disease,cerebrovascular accident.Conclusion:In clinical,We must pay attentation to the common adverse event for upadacitinib and the new PTs which were not listed in the label.Meanwhile,clinicians and pharmacists to enhance their vigilance for the outcome of serious adverse events of upadacitinib and the corresponding detection signals,such as serious pneumonia,cardiovascular disease,cerebrovascular accident.