抗CGRP/CGRPR单克隆抗体安全信号的挖掘与评价  

Mining and evaluation of safety signals for anti-CGRP/CGPRR monoclonal antibodies

作　　者：张瀛化 张思培 索元辰 白宇 王莹[1] ZHANG Yinghua;ZHANG Sipei;SUO Yuanchen;BAI Yu;WANG Ying(Department of Pharmacy,the Second Hospital of Tianjin Medical University,Tianjin 300211,China;Department of Pharmacy,Tianjin Chest Hospital,Tianjin 300222,China;School of Computer Science and Engineering,Tianjin University of Technology,Tianjin 300382,China;Hutchison MediPharma Co.,Ltd.,Shanghai 201203,China)

机构地区：[1]天津医科大学第二医院药学部,天津300211 [2]天津市胸科医院药剂科,天津300222 [3]天津理工大学计算机科学与工程学院,天津300382 [4]和记黄埔医药(上海)有限公司,上海201203

出　　处：《中国医院药学杂志》2025年第6期674-679,共6页Chinese Journal of Hospital Pharmacy

基　　金：天津市卫生健康委青年人才项目(编号:TJWJ2021QN057)。

摘　　要：目的:挖掘抗降钙素基因相关肽(calcitonin gene-related peptide,CGRP)/其受体(CGRPR)单克隆抗体药物依瑞奈尤单抗(Erenumab,EM)、加卡奈组单抗(Galcanezumab,GM)、瑞玛奈珠单抗(Fremanezumab,FM)和艾普奈珠单抗(Eptinezumab,EP)的安全警戒信号,从药物不良事件(adverse drug event,ADE)信号角度比较4种药物在安全性上的差异,为临床安全合理用药提供参考。方法:利用报告比值比法和比例报告比值法对美国FDA不良事件报告系统(the FDA adverse event reporting system,FAERS)中2020年第1季度至2023年第3季度中的4种药物ADE报告进行数据挖掘,重点评估和比较神经、皮肤、胃肠道和心血管等重点系统的安全警戒信号。结果:经筛选处理后得到以抗CGRP/CGRPR单克隆抗体为首要怀疑药物(primary suspect drug,PS)的ADE报告数分别是EM 15875例、GM 8854例、FM 2268例和EP 1983例,整理计算后得到有效ADE信号分别为46、68、43、40个;EM在胃肠和肌肉系统的风险信号强度较其他药物最显著,心血管系统风险信号最多;GM在皮肤和神经系统风险信号强度较其他药物最显著;FM在肌肉系统未见高危信号;EP在心血管系统风险信号强度较其他药物最显著;EP除妊娠的风险信号显著,未见其他高危信号,其余3种药物均有生殖系统相关ADE的发生风险。结论:临床应用抗CGRP/CGRPR单克隆抗体类药物时应加强对患者心血管事件风险的监测;女性患者应注意月经异常等现象;应用EM、GM时,应密切关注雷诺现象和肌肉不适等现象。通过对该类药物的ADE信号挖掘,分析比较了该类药物的ADE信号风险,有助于降低临床用药风险,提高临床用药选择性。OBJECTIVE To mine and analyze the safety warning signals of four anti-calcitonin gene-related peptide monoclonal antibodies(anti-CGRP/CGRPR mAbs),including the Erenumab(EM),Galcanezumab(GM),Fremanezumab(FM)and Eptinezumab(EP),and compare their safety profile by analyzing the adverse drug events(ADEs),thus providing references for rational drug use in clinical practice.METHODS All ADE reports of the four anti-CGRP mAbs were retrieved from the United States Food and Drug Administration(FDA)Adverse Event Reporting System(FAERS)database from the first quarter(Q1)of 2020 to Q3 of 2023,and the reporting odds ratio and proportional reporting ratio were analyzed.Assessment and comparisons were made between the four drugs in terms of ADRs from the nervous,skin,gastrointestinal and cardiovascular systems.RESULTS After screening,the number of ADE reports with anti-CGRP/CGRPR mAbs as the primary suspect(PS)drug was 15875 in EM,8854 in GM,2268 in FM,and 1983 in EP.After calculations,46,68,43 and 40 effective ADE signals were reported in EM,GM,FM and EP,respectively.ADE signals in the gastrointestinal system and muscular system were stronger for EM than other agents,and much more in the heart and cardiovascular system.ADE signals in the skin and nervous system were stronger for FM than other agents.High-risk ADE signals in the muscular system were not seen for FM.ADE signals in the heart and cardiovascular system were stronger for EP than other agents.Except for pregnancy,high-risk ADE signal was not detected.The remaining three drugs all reported the risk of ADE signals in the reproductive system.CONCLUSION In the clinical use of anti-CGRP/CGRPR mAbs,it is essential to monitor the risk of cardiovascular,and menstruation abnormalities in females.Attention should be paid to assess the new ADE signals,such as Raynaud's phenomenon and muscle discomfort when using EM and GM.The latest evaluation and comparison of safety about anti-CGRP/CGRPR mAbs ADE can reduce the risk of drugs and increase the selectivity of drugs.

关 键 词：降钙素基因相关肽 偏头痛 预防性治疗 安全性 比例失衡法 

分 类 号：R971.1[医药卫生—药品]