基于FAERS的托法替布超敏性及栓塞和血栓不良事件信号挖掘

Signal Mining of Tofacitinib-Related Hypersensitivity,Embolism and Thrombosis Adverse Drug Events Based on FAERS

目的为临床安全合理应用托法替布提供参考。方法提取美国食品和药物管理局(FDA)不良事件报告系统(FAERS)中2012年第4季度至2021年第4季度的托法替布药品不良事件(ADE)数据,基于标准《ICH国际医学用语词典》(MedDRA,25.0版)分析查询(SMQ)对超敏性及栓塞和血栓ADE进行信号挖掘,采用报告比值比(ROR)法、综合标准(MHRA)法,分别在SMQ层级、首选语(PT)层级进行阳性信号统计。结果提取到托法替布相关的超敏性ADE 8798个,涉及案例6994例;栓塞和血栓ADE 3102个,涉及案例2716例。SMQ层级,超敏性、栓塞和血栓ADE,两法均未检测出阳性信号。PT层级,对于超敏性ADE,两法分别检测出10,7个阳性信号,6个重叠,分别为季节性过敏、口周皮炎、过敏性鼻窦炎、口咽水疱、外阴阴道皮疹、肥大细胞活化综合征,均为新的不良反应信号;对于栓塞和血栓ADE,两法分别检测出4,2个阳性信号,2个重叠,与药品说明书所载一致。栓塞和血栓ADE患者使用托法替布平均日剂量(11.12±3.53)mg,高于世界卫生组织推荐值(10 mg)。结论托法替布可导致超敏性和肺栓塞ADE,建议临床用药时考虑其可能引起的不良反应,加强用药监护及用药教育。

Objective To provide a reference for the safe and rational application of tofacitinib in clinical practice.Methods The tofacitinib-related adverse drug events(ADEs)in the Food and Drug Administration(FDA)Adverse Event Reporting System(FAERS)from the fourth quarter of 2012 to the fourth quarter of 2021 were extracted.The ADE signals of hypersensitivity,embolism and thrombosis were mined based on the standardized MedDRA(25.0 Version)queries(SMQ).Reporting odds ratio(ROR)and Medicines and Healthcare Products Regulatory Agency(MHRA)were used to record positive signals at the SMQ level and the preferred term(PT)level,respectively.Results A total of 8798 tofacitinib-related hypersensitivity ADEs(involving 6994 cases)and 3102 tofacitinib-related embolism and thrombosis ADEs(involving 2716 cases)were extracted.At the SMQ level,no positive ADE signal of hypersensitivity,embolism and thrombosis was detected by the ROR and MHRA methods.At the PT level,ten and seven positive ADE signals of hypersensitivity were detected by the ROR and MHRA methods respectively,including six overlapping ADE signals,namely seasonal allergy,perioral dermatitis,allergic sinusitis,oropharyngeal blister,vulvovaginal rash and mast cell activation syndrome,all of which were new adverse reaction signals.At the PT level,four and two positive ADE signals of embolism and thrombosis were detected by the ROR and MHRA methods respectively,including two overlapping ADE signals,which were consistent with those in the drug instructions.The average daily dose of patients with embolism and thrombosis ADEs using tofacitinib was(11.12±3.53)mg,which was higher than the recommended dose of the World Health Organization(10 mg).Conclusion Tofacitinib can induce the ADEs of hypersensitivity and pulmonary embolism.It is suggested that we should consider the possible adverse reactions during clinical medication,and strengthen the medication monitoring and education.