奥法妥木单抗ADE信号的初步挖掘与分析  

Preliminary mining and analysis of ADE signal of ofatumumab

作　　者：杨小娟 张清文[1] 杜潇洒 董金鹏 胡一鸣 王书第 冯钰斌 YANG Xiaojuan;ZHANG Qingwen;DU Xiaosa;DONG Jinpeng;HU Yiming;WANG Shudi;FENG Yubin(Office of Clinical Trial Institution,Wanbei Coal-electricity Group General Hospital,Anhui Suzhou 234000,China;Dept.of Pharmacy,Suzhou Hospital of Anhui Medical University,Anhui Suzhou 234000,China;College of Pharmacy,Wannan Medical College,Anhui Wuhu 241002,China;Dept.of Pharmacy,Wanbei Coal-electricity Group General Hospital,Anhui Suzhou 234000,China;Dept.of Pharmacy,the First Affiliated Hospital of the University of Science and Technology of China(Anhui Provincial Hospital),Hefei 230001,China)

机构地区：[1]皖北煤电集团总医院药物临床试验机构办公室,安徽宿州234000 [2]安徽医科大学附属宿州医院药学部,安徽宿州234000 [3]皖南医学院药学院,安徽芜湖241002 [4]皖北煤电集团总医院药学部,安徽宿州234000 [5]中国科学技术大学附属第一医院(安徽省立医院)药学部,合肥230001

出　　处：《中国药房》2024年第17期2120-2125,共6页China Pharmacy

基　　金：安徽省重点研究与开发项目(No.2022e07020010)。

摘　　要：目的筛选奥法妥木单抗治疗多发性硬化症(MS)的潜在药物不良事件(ADE)信号,为临床安全用药提供参考依据。方法以“ofatumumab”及其商品名“Kesimpta”为检索关键词,筛选2009年1月至2023年12月美国FDA不良事件监测系统数据库收录的奥法妥木单抗相关不良事件(AE)报告,且该报告使用原因中包含“multiple sclerosis”字段。综合报告比值比、比例报告比值比两种方法进行ADE信号的挖掘与分析。结果共筛选出符合条件的AE报告21759份,包括62449例AE,涉及一般疾病和给药部位各种反应(15021例),神经系统疾病(9668例),感染和侵袭类疾病(5967例),伤害、中毒和手术并发症(4952例),肌肉骨骼和结缔组织疾病(4647例)等27个系统器官分类。21759份AE报告对应606个ADE信号,其中有234个阳性信号。有107个ADE阳性信号未被奥法妥木单抗说明书收录,包括流感样疾病、鼻咽炎、咳嗽、泌尿道感染、口咽痛、失眠、流涕、贫血、脱发、房颤与血小板减少等。结论临床在使用奥法妥木单抗治疗MS的过程中,除应对说明书明确收录的ADE予以足够重视外,还应对本研究筛选出的信号强度较强的ADE(如流感样疾病、血细胞减少、温度不耐受性、视神经炎与烟雾病等)格外注意。奥法妥木单抗增加的感染风险、心血管疾病风险以及其可能对呼吸系统、精神系统等造成的损害也不容忽视。OBJECTIVE To screen potential adverse drug event(ADE)signals for the treatment of multiple sclerosis(MS)with ofatumumab,and to provide reference for the safe use of drugs in clinical practice.METHODS Using“ofatumumab”and the trade name“Kesimpta”as the search keywords,adverse event(AE)reports related to ofatumumab included in FDA Adverse Event Reporting System database from January 2009 to December 2023 were screened,and their reason contained the“multiple sclerosis”;ADE signal mining and analysis were conducted by reporting odds ratio method and proportional reporting ratio method.RESULTS A total of 21759 eligible AE reports were selected,involving 62449 AE cases;27 system organ classes included general diseases and various reactions at the site of administration(15021 cases),neurological diseases(9668 cases),infectious and invasive diseases(5967 cases),injury,poisoning and surgical complications(4952 cases),musculoskeletal and connective tissue disorders(4647 cases).A total of 21759 AE reports correspond to 606 ADE signals,including 234 ADE positive signals.A total of 107 ADE positive signals were not included in drug instruction of ofatumumab,including flu-like diseases,nasopharyngitis,cough,urinary tract infection,sore throat,insomnia,runny nose,anemia,hair loss,atrial fibrillation,and thrombocytopenia,etc.CONCLUSIONS In the process of using ofatumumab for MS,sufficient attention should be paid to ADE included in drug instructions.The ADE with strong signal strength screened in this study should also be paid special attention to,such as flu-like diseases,hemocytopenia,temperature intolerance,optic neuritis,and moyamoya disease.The increased risk of infection,cardiovascular disease,and potential damage to the respiratory and spiritual systems caused by ofatumumab can not be ignored.

关 键 词：奥法妥木单抗 多发性硬化症 FAERS数据库 报告比值比法 比例报告比值比法 药物不良事件 鼻咽炎 房颤 

分 类 号：R969.3[医药卫生—药理学]