基于FAERS的阿达木单抗相关不良事件风险信号挖掘

Risk signal mining of adverse event related to adalimumab based on FAERS

目的挖掘阿达木单抗相关不良事件(AE)的风险信号,为该药的临床合理使用提供参考。方法收集美国FDA不良事件报告系统(FAERS)2015年1月1日至2021年12月31日上报的阿达木单抗相关AE数据。利用报告比值比法、英国药品和保健产品管理局综合标准法进行数据挖掘,利用《国际医学用语词典》(23.0版)药物ADR术语集中的系统器官分类(SOC)和首选术语(PT)对挖掘到的风险信号进行分类和描述。结果共检索到阿达木单抗相关AE报告149203份,其中严重AE报告65218份(43.71%);共挖掘出2660个PT,涉及27个SOC。与原发疾病相关的PT(关节痛、克罗恩病、类风湿关节炎、腹痛、骨关节炎、肠梗阻、银屑病、关节肿胀、关节炎等)较多,其次为炎症和疼痛相关的PT(操作性疼痛、炎症等);主要SOC包括各种肌肉骨骼及结缔组织疾病(68227例),胃肠系统疾病(50682例),各类损伤、中毒及手术并发症(32404例),感染及侵染类疾病(15651例),全身性疾病及给药部位各种反应(15424例)等。结论临床在使用阿达木单抗时,应注意患者可能发生的与自身免疫系统相关的反常银屑病、狼疮样综合征;同时关注严重感染、结核病、恶性肿瘤、脱髓鞘、充血性心力衰竭等AE,若发生相关AE,应及时采取干预措施;此外,还应特别关注颅内动脉瘤、卵巢囊肿、冠状动脉闭塞、甲状腺肿块等说明书中未提及的AE,以保障患者的用药安全。

OBJECTIVE To provide reference for clinical safe and rational use of adalimumab by mining the risk signals of adverse event(AE).METHODS AE reports related to adalimumab were collected from FDA adverse event reporting system(FAERS)from Jan.1st,2015 to Dec.31th,2021.The reporting odds ratio(ROR)method and the Medicines and Healthcare Products Regulatory Agency(MHRA)method were adopted to mine the AE risk signals related to adalimumab,AEs were classified and described by using the preferred system organ class(SOC)and preferred term(PT)of Medical Dictionary for Regulatory Activities(23.0).RESULTS A total of 149203 AE reports related to adalimumab were screened,among which 65218 cases(43.71%)were severe AE reports.A total of 2660 PTs were mined,involving 27 SOCs.PTs related to primary disease(arthralgia,Crohn’s disease,rheumatoid arthritis,abdominal pain,osteoarthritis,intestinal obstruction,psoriasis,joint swelling,arthritis,etc.)were more frequently reported,followed by PTs related to inflammation and pain(procedural pain,inflammation,etc.).The main SOC included musculoskeletal and connective tissue diseases(68227 cases),gastrointestinal diseases(50682 cases),injury,poisoning and procedural complications(32404 cases),infections and infestations(15651 cases),general disorders and administration site conditions(15424 cases),etc.CONCLUSIONS It is suggested to pay attention to the possible occurrence of paradoxical psoriasis and lupus-like syndrome related to the autoimmune system when using adalimumab clinically;at the same time,the attention should be paid to serious infection,tuberculosis,malignant tumors,demyelination,congestive heart failure and other AEs.If related AEs occurs,intervention measures should be taken in time.Great importance should be paid to intracranial aneurysms,ovarian cysts,coronary artery occlusion,thyroid masses and other AEs not mentioned in the instrcution,to ensure the medication safety of patients.