基于FAERS数据库的奥法妥木单抗治疗多发性硬化的不良反应事件信号挖掘与严重不良反应事件影响因素分析

Adverse event signal mining and serious adverse event influencing factors of ofatumumab in treating multiple sclerosis based on FAERS database

目的挖掘奥法妥木单抗上市后治疗多发性硬化(MS)的不良反应事件(ADE)并探究严重ADE的危险因素,为临床安全用药提供参考。方法提取FAERS数据库中奥法妥木单抗自2020年第3季度至2023年第4季度共14个季度治疗MS的ADE报告,采用报告比值比(ROR)法、比例报告比值(PRR)法、综合标准(MHRA)法对ADE信号进行挖掘分析,根据其严重程度进行分组,并分析奥法妥木单抗致严重ADE的危险因素。结果共获得奥法妥木单抗为首要怀疑药物的ADE报告75380份,挖掘阳性信号133个,涉及16个系统器官分类SOC,主要集中于全身性疾病及给药部位各种反应〔27个信号(20.15%),20542份报告(27.25%)〕、各类神经系统疾病〔23个信号(17.16%),7057份报告(9.36%)〕。对严重ADE报告进行回归分析显示,性别〔OR(95%CI)为2.496(1.777~3.504),P<0.001〕、年龄〔OR(95%CI)为1.033(1.007~1.059),P<0.001〕、体重〔OR(95%CI)为0.984(0.978~0.989),P<0.001〕是奥法妥木单抗发生严重ADE的影响因素。结论MS患者影响ADE结局的因素不同,随着年龄增长和体重减轻,更易发生严重ADE,且男性较女性更易发生严重ADE。在临床使用奥法妥木单抗过程中应根据患者年龄制定监测计划及用药方案,并加强对患者体重及营养代谢的管理,以保证患者用药安全。

Objective To explore post-marketing adverse events(ADEs)of ofatumumab in treating multiple sclerosis(MS)and to investigate the risk factors of serious ADEs,and to provide reference for the safe use of the drug in the clinic.Methods The ADE reports of ofatumumab in the FAERS database were extracted for a total of 14 quarters from the third quarter of 2020 to the fourth quarter of 2023,and the ADE signals were mined by using the report-ratio-ratio(ROR)method,the proportional report-ratio(PRR)method,and the composite criterion(MHRA)method,grouped according to their severity,and analyzed for the risk factors of severe ADEs caused by ofatumumab.Results A total of 75380 ADE reports with ofatumumab as the first suspected drug were obtained,and 133 positive signals were unearthed,involving 16 system-organ classification SOCs,mainly focusing on systemic diseases and various reactions at the site of administration[27 signals(20.15%),20542 reports(27.25%)],and various types of neurological diseases[23 signals(17.16%),7057 reports(9.36%)].Regression analysis of severe ADE reports showed that gender[OR(95%CI)2.496(1.777-3.504),P<0.001],age[OR(95%CI)1.033(1.007-1.059),P<0.001],weight[OR(95%CI)0.984(0.978-0.989),P<0.001]were the influencing factors for the occurrence of severe ADE with ofatumumab.Conclusions MS patients have different factors affecting ADE outcomes,and are more likely to have severe ADEs as their age and lose weight.In addition,male patients are more likely to have severe ADEs than female patients.In the process of clinical use of ofatumumab,monitoring programs and medication regimens should be formulated according to the patient's age.The management of the patient's body weight and nutritional metabolism should be strengthened to ensure the safety of the patients’medication.