基于美国FAERS和日本JADER数据库的内皮素受体拮抗剂不良事件信号分析

doi:10.19803/j.1672-8629.20240205

摘要/Abstract

摘要： 目的分析马昔腾坦、安立生坦和波生坦不良事件发生特点,为临床选择内皮素受体拮抗剂提供参考。方法基于美国食品药品监督管理局（FDA）不良事件报告系统（adverse event reporting system, FAERS）和日本药品不良事件报告数据库（Japanese adverse drug event report database,JADER）中2013年10月1日至2023年12月31日以马昔腾坦、安立生坦、波生坦为首要怀疑药品的所有不良事件报告,采用ROR法和IC法对内皮素受体拮抗剂相关不良事件信号进行计算,筛选阳性信号进行对比分析。采用Log-rank检验和非参数检验比较内皮素受体拮抗剂相关不良事件诱发时间差异性。结果基于2个数据库共获得马昔腾坦不良事件报告35 150例、安立生坦75 177例、波生坦22 707例。马昔腾坦、安立生坦的诱发贫血在JADER中报告数量最多,马昔腾坦、安立生坦、波生坦诱发液体潴留在FAERS中报告数量最多。波生坦肝功能异常相关信号强度显著高于马昔腾坦和安立生坦。马昔腾坦贫血相关不良事件信号强度显著高于安立生坦和波生坦。安立生坦液体潴留相关信号强度显著高于马昔腾坦和波生坦。对未成年患者进行不良事件信号挖掘发现,波生坦相较其他内皮素受体拮抗剂更容易诱发未成年患者肝功能检验异常,安立生坦更容易诱发未成年患者鼻咽不适。未成年患者使用马昔腾坦应重点关注贫血、血小板降低、肝功能指标异常、鼻衄、血压降低、低钾血症。马昔腾坦联合一氧化氮受体拮抗剂[173(IQR 40~544)]不良事件诱发时间最短,波生坦联合前列环素受体拮抗剂[632.5(IQR 222.75~1 225.5)]不良事件诱发时间最长。结论不同内皮素受体拮抗剂不良事件风险信号强度和不良事件诱发时间可能存在差异。对患者应开展个体化用药和监护,减少可能的不良反应,保障患者用药安全。

关键词: 内皮素受体拮抗剂, 马昔腾坦, 安立生坦, 波生坦, 药品不良反应/药品不良事件, 数据挖掘, 美国食品药品监督管理局不良事件报告系统, 日本药品不良事件报告数据库

Abstract: Objective Analysis of the occurrence characteristics of adverse events of macitentan, ambrisentan and bosentan, in order to provide a reference for the clinical selection of endothelin receptor antagonists. Methods Based on all adverse event reports in the FDA Adverse Event Reporting System(FAERS) and Japanese Adverse Drug Event Report(JADER) database from October 1, 2013 through December 31, 2023. We used the reporting odds ratio (ROR) method and the information component (IC) method to calculate the signals of endothelin receptor antagonist-associated adverse events. The positive signals were analyzed and compared. Log-rank test and nonparametric test were used to compare the differences in the time to induce ADE of endothelin receptor antagonists. Results Based on two database, total of 35 150 adverse event reports were obtained for macitentan, 75 177 for ambrisentan, and 22 707 for bosentan. Macitentan and ambrisentan-induced anaemia was reported in highest numbers in JADER, and macitentan, ambrisentan and bosentan-induced fluid retention was reported in highest numbers in FAERS. Bosentan hepatic impairment PT signal intensity was significantly higher than that of macitentan and irisentan. Anemia signal ranked highest in JADER and fluid retention signal ranked highest in FAERS. Bosentan hepatic impairment PT signal strength was significantly higher than that of macitentan and irisentan. Macitentan anemia PT signal strength was significantly higher than that of anrisentan and bosentan. Anlisentan fluid retention PT signal strength was significantly higher than that of macitentan and bosentan. Adverse event signalling in minor patients revealed that bosentan was more likely to induce liver function test abnormalities in minor patients than other endothelin receptor antagonists. Ambrisentan was more likely to induce nasopharyngeal discomfort in minor patients. The use of macitentan in underage patients should focus on anaemia, thrombocytopenia, abnormal liver function tests, epistaxis, decreased blood pressure, and hypokalaemia. Macitentan combined with nitric oxide synthase inhibitor [173 (IQR 40~544)] is the fastest combination regimen to induce adverse events, and bosentan combined with prostacyclin receptor antagonistsa [632.5 (IQR 222.75~1 225.5)] had the longest time for the induction of adverse events. Conclusion There are differences in the signal intensity of risk of adverse events and the time of adverse event induction for different endothelin receptor antagonists. Individualized dosing and monitoring of patients should be carried out to reduce possible adverse events and ensure patient safety.

Key words: endothelin receptor antagonists, macitentan, ambrisentan, bosentan, adverse drug reaction/event, data mining, FAERS, JADER

中图分类号:

吴凡, 付林杰, 祝赫, 徐梦艳. 基于美国FAERS和日本JADER数据库的内皮素受体拮抗剂不良事件信号分析[J]. 中国药物警戒, 2024, 21(9): 1056-1063.

WU Fan, FU Linjie, ZHU He, XU Mengyan. Signal detection of adverse reaction of endothelin receptor antagonists based on FAERS and JADER database[J]. Chinese Journal of Pharmacovigilance, 2024, 21(9): 1056-1063.

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