Mining and analysis of adverse drug event signals related to mepolizumab

CHEN Yaoxin; WU Shaoxing; LI Haoxuan; XU Yinji

doi:10.6039/j.issn.1001-0408.2023.11.17

您当前的位置：

首页 >

文章列表页 >

Mining and analysis of adverse drug event signals related to mepolizumab

更新时间：2025-09-27

- Mining and analysis of adverse drug event signals related to mepolizumab
- ZHONGGUO YAOFANG Vol. 34, Issue 11, Pages: 1374-1378(2023)
- 作者机构：
  
  1.广州中医药大学第二临床医学院，广州　510405
  2.广东省中医院呼吸与危重症医学科，广州　510120
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.11.17
  CLC： R969.3;R976
- Received：02 November 2022，
  
  Revised：2023-05-18，
  
  Accepted：18 May 2023，
  
  Published：15 June 2023
- 稿件说明：
移动端阅览
陈耀鑫,伍绍星,李浩轩,等.美泊利单抗相关不良事件信号的挖掘与分析[J].中国药房,2023,34(11):1374-1378.

CHEN Yaoxin,WU Shaoxing,LI Haoxuan,et al.Mining and analysis of adverse drug event signals related to mepolizumab[J].ZHONGGUO YAOFANG,2023,34(11):1374-1378.
陈耀鑫,伍绍星,李浩轩,等.美泊利单抗相关不良事件信号的挖掘与分析[J].中国药房,2023,34(11):1374-1378. DOI： 10.6039/j.issn.1001-0408.2023.11.17.

CHEN Yaoxin,WU Shaoxing,LI Haoxuan,et al.Mining and analysis of adverse drug event signals related to mepolizumab[J].ZHONGGUO YAOFANG,2023,34(11):1374-1378. DOI： 10.6039/j.issn.1001-0408.2023.11.17.

摘要

目的

为临床合理使用美泊利单抗提供参考。

方法

采用报告比值比法和贝叶斯可信区间递进神经网络法，对2016年第1季度至2022年第3季度美国FDA不良事件报告系统中有关美泊利单抗的药品不良事件（ADE）报告进行信号挖掘与分析。

结果

共提取到以美泊利单抗为首要怀疑药物的ADE报告57 501份，涉及16 358例患者，其中男性所占比例（23.51%）低于女性（50.48%）；报告国家以美国（51.91%）和加拿大（29.94%）为主；消费者（71.18%）是主要上报人群。挖掘出172个ADE阳性信号，主要涉及呼吸系统、胸及纵隔疾病（41.63%），感染及侵染类疾病（14.16%）等13个系统器官分类。共有60个高风险信号，其中15个为美泊利单抗药品说明书明确提及或相关的药品不良反应，45个（如哮喘危象、痰变色、脓痰、一般性疾病引起的睡眠障碍等）为新的高风险信号；各有11个高风险信号有性别差异或年龄差异。

结论

临床应用美泊利单抗时，除药品说明书中提及的不良反应外，还应重点关注痰液性质的改变、痛性呼吸、睡眠障碍等。

Abstract

OBJECTIVE

To provide reference for rational clinical use of mepolizumab.

METHODS

The reporting odds ratio method and Bayesian confidence propagation neural network method were used to conduct signal mining and analysis of adverse drug event （ADE） reports related to mepolizumab in the United States Food and Drug Administration Adverse Event Reporting System from the first quarter of 2016 to the third quarter of 2022.

RESULTS

A total of 57 501 ADE reports were extracted with mepolizumab as the primary suspect drug， involving 16 358 patients. Among these reports， the proportion of males （23.51%） was lower than females （50.48%）. The reporting countries were primarily the United States （51.91%） and Canada （29.94%）. Consumers （71.18%） constituted the main reporting population. A total of 172 ADE-positive signals were identified， mainly involving 13 system organ classes such as the respiratory， thoracic and mediastinal disorders （41.63%）， as well as infectious and parasitic diseases （14.16%）. There were 60 high-risk signals， including 15 that were explicitly mentioned or related to adverse reactions in the drug instructions of mepolizumab and 45 signals （such as asthmatic crisis， sputum discoloured， purulent sputum， sleep disorder due to a general medical condition） were newly identified high-risk signals. Among them， 11 high-risk signals exhibited gender or age differences.

CONCLUSIONS

When clinically using mepolizumab， in addition to the adverse reactions mentioned in the drug instruction， special attention should also be given to changes in the nature of sputum， painful respiration， and sleep disorders.

关键词

Keywords

references

CAVALIERE C ， FRATI F ， RIDOLO E ， et al . The spectrum of therapeutic activity of mepolizumab [J ] . Expert Rev Clin Immunol ， 2019 ， 15 （ 9 ）： 959 - 967 .

THOMPSON C A . Mepolizumab approved as add-on long-term therapy for severe asthma [J ] . Am J Health Syst Pharm ， 2015 ， 72 （ 24 ）： 2125 .

U.S. FDA . Mepolizumab （NUCALA） highlights of prescribing information [EB/OL ] . [ 2022-10-25 ] . https：//www.ema.europa.eu/en/documents/product-information/nucala-epar-product-infor-mation_en.pdf https://www.ema.europa.eu/en/documents/product-information/nucala-epar-product-infor-mation_en.pdf .

European Medicines Agency . Nucala ，mepolizumab. Summary of product characteristics[EB/OL ] . [ 2022-10-25 ] . https：//www.ema.europa.eu/en/medicines/human/EPAR/nucala https://www.ema.europa.eu/en/medicines/human/EPAR/nucala .

钟思雨，田燕，肖桂荣，等 . 美泊利单抗适应证研究进展 [J ] . 中国药业， 2022 ， 31 （ 13 ）： 128， Ⅰ 0001 -Ⅰ0005.

U.S. FDA . FDA Adverse Event Reporting System （FAERS） quarterly data extract files [EB/OL ] . [ 2022-12-05 ] . https：//fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html .

罗宝章，钱轶峰，叶小飞，等 . 药物不良反应信号检测方法的现状与展望 [J ] . 药学服务与研究， 2009 ， 9 （ 4 ）： 255 - 260 .

NORÉN G N ， BATE A ， ORRE R ， et al . Extending the methods used to screen the WHO drug safety database towards analysis of complex associations and improved accuracy for rare events [J ] . Stat Med ， 2006 ， 25 （ 21 ）： 3740 - 3757 .

BATE A ， LINDQUIST M ， EDWARDS I R ， et al . A Baye- sian neural network method for adverse drug reaction signal generation [J ] . Eur J Clin Pharmacol ， 1998 ， 54 （ 4 ）： 315 - 321 .

VAN PUIJENBROEK E P ， BATE A ， LEUFKENS H G ， et al . A comparison of measures of disproportionality for signal detection in spontaneous reporting systems for adverse drug reactions [J ] . Pharmacoepidemiol Drug Saf ， 2002 ， 11 （ 1 ）： 3 - 10 .

GUAN Y Y ， JI L ， ZHENG L ， et al . Development of a drug risk analysis and assessment system and its application in signal excavation and analysis of 263 cases of fluoroquinolone-induced adverse reactions [J ] . Front Pharmacol ， 2022 ， 13 ： 892503 .

陈琪莹，陈添玉，李毅敏 . 基于FAERS对依洛尤单抗安全警戒信号的挖掘与评价 [J ] . 中国新药杂志， 2021 ， 30 （ 17 ）： 1627 - 1632 .

PAVORD I D ， BEL E H ， BOURDIN A ， et al . From DREAM to REALITI-A and beyond：mepolizumab for the treatment of eosinophil-driven diseases [J ] . Allergy ， 2022 ， 77 （ 3 ）： 778 - 797 .

KHATRI S ， MOORE W ， GIBSON P G ， et al . Assessment of the long-term safety of mepolizumab and durability of clinical response in patients with severe eosinophilic asthma [J ] . J Allergy Clin Immunol ， 2019 ， 143 （ 5 ）： 1742 - 1751 .

CHAPMAN K R ， ALBERS F C ， CHIPPS B ， et al . The clinical benefit of mepolizumab replacing omalizumab in uncontrolled severe eosinophilic asthma [J ] . Allergy ， 2019 ， 74 （ 9 ）： 1716 - 1726 .

DOMINGO RIBAS C ， CARRILLO DÍAZ T ， BLANCO APARICIO M ， et al . Real world effectiveness and safety of mepolizumab in a multicentric Spanish cohort of asthma patients stratified by eosinophils：the REDES study [J ] . Drugs ， 2021 ， 81 （ 15 ）： 1763 - 1774 .

XIE M ， LIU X ， CAO X ， et al . Trends in prevalence and incidence of chronic respiratory diseases from 1990 to 2017 [J ] . Respir Res ， 2020 ， 21 （ 1 ）： 49 .

杨蓉 . 美泊利单抗治疗重症嗜酸性粒细胞哮喘的疗效及安全性的Meta分析 [D ] . 太原：山西医科大学， 2022 .

DUNICAN E M ， ELICKER B M ， GIERADA D S ， et al . Mucus plugs in patients with asthma linked to eosinophilia and airflow obstruction [J ] . J Clin Invest ， 2018 ， 128 （ 3 ）： 997 - 1009 .

FAHY J V ， DICKEY B F . Airway mucus function and dysfunction [J ] . N Engl J Med ， 2010 ， 363 （ 23 ）： 2233 - 2247 .

VAHLE J L . Immunogenicity and immune complex disease in preclinical safety studies [J ] . Toxicol Pathol ， 2018 ， 46 （ 8 ）： 1013 - 1019 .

U.S. FDA . Immunogenicity testing of therapeutic protein products：developing and validating assays for antidrug antibody detection [EB/OL ] . [ 2022-10-25 ] . https：//www.fda.gov/media/119788/download https://www.fda.gov/media/119788/download .

Views

216

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Pharmaceutical monitoring and analysis of a case of severe systemic allergic reaction caused by Wujia shenghua capsules during the postpartum period

Mining and analysis of adverse drug event signals related to macitentan

Signal mining and analysis of selinexor adverse events

Mining and analysis of adverse drug events signals of nilotinib based on FDA adverse event database

Mining and analysis of ADE signals of romiplostim and eltrombopag based on FAERS database

Related Author

ZHAO Mingming

YE Yiqing

CHEN Xinyao

CHEN Yaoxin

WU Zhenhu

XU Yinji

XU Mengdan

GU Hangye

Related Institution

Dept. of Pharmacy， Jilin Branch， Women’s Hospital， Zhejiang University School of Medicine

Dept. of Pharmacy， Women’s Hospital， Zhejiang University School of Medicine

Dept. of Respiratory and Critical Care Medicine， Guangdong Provincial Hospital of Chinese Medicine

School of Public Health， Sun Yat-sen University

Key Specialty of Clinical Pharmacy， the First Affiliated Hospital of Guangdong Pharmaceutical University

⁰