肿瘤坏死因子抑制剂相关吉兰-巴雷综合征:基于FAERS的风险信号挖掘与评价

Tumor Necrosis Factor Inhibitors and Guillain-Barre Syndrome:Data Mining and Evaluation of Risk Signals Based on FAERS

目的梳理肿瘤坏死因子抑制剂(TNFis)相关吉兰-巴雷综合征(GBS)的特点,并对其进行风险信号挖掘与评价,为临床安全用药提供参考。方法提取2004年第一季度至2020年第一季度美国食品药品管理局不良事件报告系统(FAERS)中以依那西普、英夫利西单抗、阿达木单抗、培塞利珠单抗、戈利木单抗5种TNFis为首要怀疑药品的GBS不良事件数据,对报告、患者、事件的主要特征进行描述,并采用报告比值比法(ROR)进行风险信号检测,检出阈值为报告数≥3且ROR的95%置信区间(CI)下限>1。结果共收集TNFis相关GBS不良事件报告病例330例,59.70%来源于美洲,75.76%由医疗卫生专业人士上报;患者女性略多于男性,平均年龄(51.67±15.96)岁,原发病以关节炎性病变(56.06%)最多;使用TNFis后GBS中位发生时间为248 d,导致入院或住院时间延长的病例占67.58%,死亡病例占4.55%。5种TNFi均有GBS报告,经ROR法分析,英夫利西单抗和阿达木单抗产生GBS风险信号,其中英夫利西单抗信号最强[ROR 2.70,95%CI(2.15,3.40)]。结论通过FAERS数据挖掘,发现了TNFis相关GBS风险信号并可能存在药品之间的差别,在临床用药中需引起重视,同时为进一步加强药物警戒工作奠定基础。

Objective To investigate the characteristics of Guillain-Barrésyndrome(GBS)adverse events related to tumor necrosis factor inhibitors(TNFis)and to mine and evaluate their risk signals,in order to provide references for the safety of drug use.Methods Data of GBS adverse event reports of etanercept,infliximab,adalimumab,certolizumab,and golimumab as the primary suspect drugs were extracted from US Food and Drug Administration Adverse Event Reporting System(FARES)between the 1 st Quarter 2004 to the 1 st Quarter 2020.Main characteristics of these adverse event reports were described.Risk signals were analyzed by using the reporting odds ratio(ROR)method,and a signal generated when the report numbers≥3 and the lower limit of 95%CI of ROR>1.Results A total of 330 adverse event reports of GBS for TNFis were collected,among which 59.70%were from America and 75.76%were reported by health professionals.Females were slightly more than males,with an average age of 51.67±15.96 years old,and 56.06%of primary diseases were inflammatory lesions of arthrosis.The median GBS onset time was 248 days after receiving TNFis.Among the 330 cases,67.58%cases were hospitalized(initial or prolonged)and 4.55%cases resulted in death.With respect to drugs,all five TNFis were reported as primary suspect drugs for GBS,while ROR analysis showed risk signals for infliximab and adamumab,and infliximab had the strongest signal[ROR 2.70,95%CI(2.15,3.40)].Conclusion Analysis of FAERS data helped identify the potential risks of GBS by TNFis,which may differ among varieties.More attention should be paid to these adverse events and further pharmacovigilance is required.