基于真实世界数据的CGRP靶向药物不良事件的对比分析

Comparative analysis of CGRP targeted drugs-related adverse events based on real world data

目的 对比分析降钙素基因相关肽(CGRP)靶向药物上市后的不良事件,为患者药物选择和临床安全用药提供参考。方法 收集美国食品药品监督管理局(FDA)不良事件报告系统(FAERS)中自药品上市时间至2023年9月30日的原始数据,采用报告比值比法(ROR)和贝叶斯可信区间递进神经网络法(BCPNN),对比分析小分子CGRP受体拮抗剂(吉泮类)和CGRP单抗类药物的不良事件信号。结果 吉泮类不良事件信号共计176个(报告例数10 569),单抗类不良事件信号共计401个(报告例数87 605)。所有CGRP靶向药物均存在药物无效和治疗效果下降的不良事件。吉泮类共有的不良事件信号包括恶心、嗜睡和眩晕,单抗类共有的不良事件信号为注射(或输液)部位的各种反应。存在FDA说明书中未记载的多个不良事件信号,有些信号是某类药物所特有的,如阿托吉泮的便秘,瑞美吉泮的上腹痛和咽部肿胀等,乌布吉泮的胸痛、颈痛和心悸等,加卡奈珠单抗的眩晕和体重增加,瑞玛奈珠单抗的肿舌和耳鸣,艾普奈珠单抗的咽喉刺激、鼻充血和超敏反应等。结论 CGRP靶向药物的不良事件既有共性也有各自的特性,对于说明书未记载的不良事件,临床应予以关注并指导患者安全用药。

Objective To provide references for patients to select drugs and clinical safe use through comparative analysis of post-marketing adverse events of CGRP-targeted drugs.Methods The original data from the FDA Adverse Event Reporting System from the time of drug launch to September 30,2023 were collected.The reporting odds ratio(ROR)and the Bayesian confidence propagation neural network(BCPNN)were used to compare and analyze the adverse event signals of small molecule CGRP receptor antagonists(gepants)and CGRP monoclonal antibodies.Results There were a total of 176 adverse event signals for gepants(10569 reported cases),and 401 adverse event signals for monoclonal antibodies(87605 reported cases).All CGRP-targeted drugs had adverse events of drug ineffectiveness and decreased therapeutic efficacy.The common adverse event signals of gepants included nausea,somnolence,and vertigo,while the common adverse event signals of monoclonal antibodies were injection(or infusion)site reactions.Multiple adverse event signals were not recorded in the FDA instructions and some signals were specific to a certain type of drug,such as constipation of atogepant,upper abdominal pain and pharyngeal swelling of rimegepant,chest pain,neck pain,and palpitations of ubrogepant,vertigo and weight gain of galcanezumab,swollen tongue and tinnitus of fremanezumab,and throat irritation,nasal congestion,and hypersensitivity reactions of eptinezumab.Conclusion Adverse events of CGRP-targeted drugs have both commonalities and individual characteristics.Clinical attention should be paid to adverse events not listed in the instructions,and patients should be guided to use these drugs safely.