基于FAERS数据库的特立帕肽与阿巴洛肽不良事件信号挖掘

Adverse Drug Events Signal Mining of Teriparatide and Abaloparatide Based on FAERS Data-base

关键词:  特立帕肽  阿巴洛肽  骨质疏松  美国FDA不良反应报告系统  药物不良事件  信号挖掘

Key words:  teriparatide  abaloparatide  osteoporosis  FDA adverse event reporting system  adverse drug events  signal mining

摘要:

目的 挖掘特立帕肽、阿巴洛肽的药物不良事件(adverse drug event,ADE)信号,为临床安全用药及合理选药提供参考。方法 提取FAERS数据库特立帕肽2004年第1季度-2021年第3季度、阿巴洛肽自2017年上市至2021年第3季度的ADE报告数据,采用报告比值比法(reporting odds ratio,ROR)和比例报告比法(proportional report ratio,PRR)进行数据挖掘,分析两药相关ADE报告并统计报告人群的性别、年龄、严重ADE等基本信息。结果 排除各类损伤、中毒及操作并发症,各类手术及医疗操作,以及产品问题和社会问题等与药物无关的信号后,得到特立帕肽相关的ADE报告有88 474例,有效信号为600个,信号涉及22个系统器官;阿巴洛肽相关的ADE报告有12 286例,有效信号为137个,累及系统器官17个。按发生频次排序,2种药物发生最多的ADE分别是头晕(4 896例)和头痛(1 485例);按信号强度排序,特立帕肽报告的尿氨基端肽升高(ROR:135.867)和阿巴洛肽报告的血清I型原胶原蛋白氨基端前肽降低(ROR:881.625)居于首位,说明书中均未提及。两药ADE信号均集中于各类肌肉骨骼和结缔组织疾病,全身性疾病及给药部位各种反应。结论 特立帕肽与阿巴洛肽上市以来的应用总体较为安全,引起的常见不良反应大多较为轻微,但治疗期间仍需特别注意罕见不良反应的发生情况并定期检测血钙、血尿酸等实验室指标,提防骨骼系统ADE。

Abstract:

OBJECTIVE To excavate the adverse drug events(ADE) signals of teriparatide and abaloparatide, and to provide reference for clinical medication safety and rational selection. METHODS All ADE reports of teriparatide from the first quarter of 2004 to the third quarter of 2021 and abaloparatide from the launch of 2017 to the third quarter of 2021 in FAERS database were mined using reporting odds ratio(ROR) and proportional report ratio(PRR). Meanwhile, the basic information such as gender, age and severe ADE outcome of the patients were statistically reported. RESULTS After excluding all kinds of injuries, poisoning and operation complications, all kinds of operations and medical operations, product problems and social problems and other unrelated signals, there were 88 474 ADE reports related to teriparatide, and 600 effective signals were obtained, the signals involved 22 system organs; 12 286 cases of abaloparatide-related ADE reports, 137 effective signals and 17 system organs were mined. According to the occurrence frequency, the most common ADEs for the two drugs were dizziness (4 896 cases) and headache(1 485 cases). According to the signal strength, N-telopeptide urine increased of teriparatide(ROR:135.867) and serum procollagen type I N-terminal propeptide decreased of abaloparatide(ROR:881.625) rank first, both which were not reported in the drug instructions. The ADE signals of both drugs were concentrated in musculoskeletal and connective tissue conditions, general disorders and administration site conditions. CONCLUSION The application of teriparatide and abaloparatide have been relatively safe, and most of the common ADE are relatively mild. However, special attention should be paid to the occurrence of rare ADE. Laboratory index such as blood calcium, blood uric acid should be regularly detected, meanwhile, watch out for the occurrence of adverse reactions in the skeletal system.