Signal mining and evaluation of adverse events of four biological agents for the treatment of inflammatory bowel disease

LIU Defeng; LIU Rui; QIAN Yan; DU Qingqing

doi:10.6039/j.issn.1001-0408.2024.12.17

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Signal mining and evaluation of adverse events of four biological agents for the treatment of inflammatory bowel disease

更新时间：2025-09-26

- Signal mining and evaluation of adverse events of four biological agents for the treatment of inflammatory bowel disease
- ZHONGGUO YAOFANG Vol. 35, Issue 12, Pages: 1511-1516(2024)
- 作者机构：
  
  重庆医科大学附属第二医院药学部，重庆　400010
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.12.17
  CLC： R969.3;S859.79+
- Received：03 November 2023，
  
  Revised：2024-05-21，
  
  Accepted：29 May 2024，
  
  Published：30 June 2024
- 稿件说明：
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刘德凤,刘蕊,钱妍,等.4种治疗炎症性肠病生物制剂的不良事件信号挖掘与评价[J].中国药房,2024,35(12):1511-1516.

LIU Defeng,LIU Rui,QIAN Yan,et al.Signal mining and evaluation of adverse events of four biological agents for the treatment of inflammatory bowel disease[J].ZHONGGUO YAOFANG,2024,35(12):1511-1516.
刘德凤,刘蕊,钱妍,等.4种治疗炎症性肠病生物制剂的不良事件信号挖掘与评价[J].中国药房,2024,35(12):1511-1516. DOI： 10.6039/j.issn.1001-0408.2024.12.17.

LIU Defeng,LIU Rui,QIAN Yan,et al.Signal mining and evaluation of adverse events of four biological agents for the treatment of inflammatory bowel disease[J].ZHONGGUO YAOFANG,2024,35(12):1511-1516. DOI： 10.6039/j.issn.1001-0408.2024.12.17.

摘要

目的

挖掘4种治疗炎症性肠病（IBD）生物制剂的药品不良事件（ADE）信号，为临床安全用药提供参考。

方法

收集美国FDA不良事件报告系统2004年第1季度至2022年第4季度上报的英夫利昔单抗、阿达木单抗、乌司奴单抗、维得利珠单抗的ADE数据，并采用报告比值比法（ROR）和比例报告比法（PRR）进行信号挖掘，对ADE的系统器官分类（SOC）进行分类统计。结果与

结论

分别检索到上述4种生物制剂ADE报告65 173、247 894、37 596、6 134份，生成1 664、1 731、588、303个ADE信号，分别累及27、27、24、26个SOC。英夫利昔单抗以各种肌肉骨骼及结缔组织疾病的ADE报告数最多，播散型结核信号强度较强；阿达木单抗以全身性疾病及给药部位各种反应的ADE报告数最多，注射部位丘疹信号强度较强；乌司奴单抗以各类损伤、中毒及操作并发症的ADE报告数最多，潜伏性结核信号强度稍强；维得利珠单抗以全身性疾病及给药部位各种反应的ADE报告数最多，治疗反应时间缩短的信号强度较强。临床用药时，除关注常见ADE外，对英夫利昔单抗应警惕滑膜炎、基底细胞癌，对阿达木单抗应警惕滑膜炎、疝气，对乌司奴单抗应警惕肝胆系统疾病，对维得利珠单抗应警惕便血、排便频率增加等药品说明书未提及的ADE；除乌司奴单抗外，对其他3种药物还需注意与妊娠相关的ADE。

Abstract

OBJECTIVE

To provide reference for safe drug use in the clinic by mining the adverse drug event （ADE） signals of 4 kinds of biological agents for the treatment of inflammatory bowel disease （IBD）.

METHODS

ADE data of infliximab， adalimumab， ustekinumab and vedolizumab were collected from the FDA adverse event reporting system between the first quarter in 2004 and the fourth quarter in 2022， and were mined by using reporting odds ratio （ROR） method and proportional reporting ratio （PRR） method. The system organ class （SOC） was used for the classification and statistics of drug ADE terminology. RESULTS &

CONCLUSIONS

A total of 65 173， 247 894， 37 596 and 6 134 ADE reports were retrieved for the above 4 biologic agents， involving 1 664， 1 731， 588， 303 ADE signals and 27， 27， 24， 26 SOC， respectively. The largest number of ADE reported of infliximab were various musculoskeletal and connective tissue diseases， and the signal intensity of disseminated tuberculosis was stronger. The largest number of ADE reported of adalimumab were systemic disease and various reactions at the administration site， and the signal intensity of papular at the injection site was stronger. The largest number of ADE reported of ustekinumab were various injuries， poisoning and operation complications， and the signal intensity of latent tuberculosis was slightly stronger. The largest number of ADE reported of vedolizumab were systemic diseases and various reactions at the administration site， and the signal intensity of shorter treatment response time was stronger. When clinically administering the four drugs， it is crucial to pay close attention to common ADEs and other ADE not mentioned in the drug label. For infliximab， clinicians should exercise caution due to the potential risk of synovitis and basal cell carcinoma； when prescribing adalimumab， caution should be exercised due to ADEs related to synovitis and hernia； for ustekinumab， the ADE associated with hepatobiliary diseases should be vigilant； for vedolizumab， clinicians should be vigilant for blood in the stool， increasing frequency of defecation. Except for ustekinumab， the other 3 biological agents also require attention for ADE associated with pregnancy.

关键词

Keywords

references

GORDON H ， BIANCONE L ， FIORINO G ， et al . ECCO guidelines on inflammatory bowel disease and malignancies [J ] . J Crohns Colitis ， 2023 ， 17 （ 6 ）： 827 - 854 .

NG S C ， KAPLAN G G ， TANG W ， et al . Population density and risk of inflammatory bowel disease：a prospective population-based study in 13 countries or regions in Asia-Pacific [J ] . Am J Gastroenterol ， 2019 ， 114 （ 1 ）： 107 - 115 .

余光，罗和生 . 生物制剂治疗炎症性肠病的安全性评价 [J ] . 胃肠病学和肝病学杂志， 2016 ， 25 （ 2 ）： 226 - 230 .

YU G ， LUO H S . The safety of TNF-α in treatment of the inflammatory bowel disease [J ] . Chin J Gastroenterol Hepatol ， 2016 ， 25 （ 2 ）： 226 - 230 .

BATE A ， EVANS S J W . Quantitative signal detection using spontaneous ADR reporting [J ] . Pharmacoepidemiol Drug Saf ， 2009 ， 18 （ 6 ）： 427 - 436 .

EVANS S J ， WALLER P C ， DAVIS S . Use of proportional reporting ratios（PRRs）for signal generation from spontaneous adverse drug reaction reports [J ] . Pharmacoepidemiol Drug Saf ， 2001 ， 10 （ 6 ）： 483 - 486 .

李长龙，舒家华，李国兴，等 . 4个进口PD-1/PD-L1抑制剂不良反应信号的挖掘与评价 [J ] . 中国药房， 2022 ， 33 （ 7 ）： 873 - 878 .

LI C L ， SHU J H ， LI G X ， et al . Excavation and evaluation of adverse reaction signals of 4 kinds of imported PD-1/PD-L1 inhibitors [J ] . China Pharm ， 2022 ， 33 （ 7 ）： 873 - 878 .

中华医学会消化病学分会炎症性肠病学组 . 炎症性肠病诊断与治疗的共识意见：2018年·北京 [J ] . 中国实用内科杂志， 2018 ， 38 （ 9 ）： 796 - 813 .

Inflammatory Bowel Disease Group，Chinese Society of Gastroenterology，Chinese Medical Association . Chinese consensus on diagnosis and treatment of inflammatory bowel disease：Beijing，2018 [J ] . Chin J Pract Intern Med ， 2018 ， 38 （ 9 ）： 796 - 813 .

LOPHAVEN S N ， LYNGE E ， BURISCH J . The incidence of inflammatory bowel disease in Denmark 1980-2013：a nationwide cohort study [J ] . Aliment Pharmacol Ther ， 2017 ， 45 （ 7 ）： 961 - 972 .

GOODMAN W A ， ERKKILA I P ， PIZARRO T T . Sex matters：impact on pathogenesis，presentation and treatment of inflammatory bowel disease [J ] . Nat Rev Gastroenterol Hepatol ， 2020 ， 17 （ 12 ）： 740 - 754 .

WANG R ， LI Z Q ， LIU S J ， et al . Global，regional and national burden of inflammatory bowel disease in 204 countries and territories from 1990 to 2019：a systematic analysis based on the global burden of disease study 2019 [J ] . BMJ Open ， 2023 ， 13 （ 3 ）： e065186 .

LEWIS J D ， PARLERR L E ， JONSSON F M ， et al . Incidence，prevalence，and racial and ethnic distribution of inflammatory bowel disease in the United States [J ] . Ga-stroenterology 2023 ， 165 （ 5 ）： 1197 - 1205 .

LICHTENSTEIN L ， RON Y ， KIVITY S ， et al . Infliximab-related infusion reactions：systematic review [J ] . J Crohns Colitis ， 2015 ， 9 （ 9 ）： 806 - 815 .

周有连，陈烨 . 英夫利昔单抗治疗炎症性肠病的疗效及影响因素分析 [J ] . 南方医科大学学报， 2013 ， 33 （ 12 ）： 1833 - 1838 .

ZHOU Y L ， CHEN Y . Efficacy of infliximab in treatment on inflammatory bowel disease and factors affecting the therapeutic effect [J ] . J South Med Univ ， 2013 ， 33 （ 12 ）： 1833 - 1838 .

O’MEARA S ， NANDA K S ， MOSS A C . Antibodies to infliximab and risk of infusion reactions in patients with inflammatory bowel disease：a systematic review and meta-analysis [J ] . Inflamm Bowel Dis ， 2014 ， 20 （ 1 ）： 1 - 6 .

BIANCONE L ， ANNESE V ， ARDIZZONE S ， et al . Safety of treatments for inflammatory bowel disease：clinical practice guidelines of the Italian group for the study of inflammatory bowel disease（IG-IBD） [J ] . Dig Liver Dis ， 2017 ， 49 （ 4 ）： 338 - 358 .

中国医药教育协会炎症性肠病专业委员会 . 中国炎症性肠病生物制剂治疗专家建议：试行 [J/OL ] . 中华消化病与影像杂志（电子版）， 2021 ， 11 （ 6 ）： 244 - 256 （ 2021-12-01 ）[ 2023-10-12 ] . https：//zhxhbyyxzz.cma-cmc.com.cn/CN/10.3877/cma.j.issn.2095-2015.2021.06.002.DOI：10.3877/cma.j.issn.2095-2015.2021.06.002 https://zhxhbyyxzz.cma-cmc.com.cn/CN/10.3877/cma.j.issn.2095-2015.2021.06.002.DOI:10.3877/cma.j.issn.2095-2015.2021.06.002 .

Inflammatory Bowel Disease Professional Committee of China Medical Education Association . Consensus on biological agents in treating patients with inflammatory bowel disease in China [J/OL ] . Chin J Dig Med Imageology（Electron Ed）， 2021 ， 11 （ 6 ）： 244 - 256 （ 2021-12-01 ）[ 2023-10-12 ] . https：//zhxhbyyxzz.cma-cmc.com.cn/CN/10.3877/cma.j.issn.2095-2015.2021.06.002.DOI：10.3877/cma.j.issn.2095-2015.2021.06.002 https://zhxhbyyxzz.cma-cmc.com.cn/CN/10.3877/cma.j.issn.2095-2015.2021.06.002.DOI:10.3877/cma.j.issn.2095-2015.2021.06.002 .

CONRAD C ， DOMIZIO J D ， MYLONAS A ， et al . TNF blockade induces a dysregulated type Ⅰ interferon re-sponse without autoimmunity in paradoxical psoriasis [J ] . Nat Commun ， 2018 ， 9 （ 1 ）： 25 .

KREMENEVSKI I ， SANDER O ， STICHERLING M ， et al . Paradoxical reactions to biologicals in chronic inflammatory systemic diseases [J ] . Dtsch Arztebl Int ， 2022 ， 119 （ 6 ）： 88 - 95 .

MAGRÌ S ， CHESSA L ， DEMURTAS M ， et al . Review article：safety of new biologic agents for inflammatory bowel disease in the liver [J ] . Eur J Gastroenterol Hepatol ， 2021 ， 33 （ 5 ）： 623 - 630 .

NIH . LiverTox：clinical and research information on drug-induced liver injury [EB/OL ] .（ 2020-04-20 ）[ 2023-10-12 ] . https：//www.ncbi.nlm.nih.gov/books/NBK548014/ https://www.ncbi.nlm.nih.gov/books/NBK548014/ .

梁瑜，孙加琳，孟真，等 . 维得利珠单抗致34例不良反应文献分析 [J ] . 中国医院药学杂志， 2022 ， 42 （ 12 ）： 1243 - 1248 .

LIANG Y ， SUN J L ， MENG Z ， et al . Literature analysis of 34 cases of adverse drug reactions induced by vedolizumab [J ] . Chin J Hosp Pharm ， 2022 ， 42 （ 12 ）： 1243 - 1248 .

GISBERT J P ， CHAPARRO M . Safety of new biologics（vedolizumab and ustekinumab）and small molecules（to facitinib）during pregnancy：a review [J ] . Drugs ， 2020 ， 80 （ 11 ）： 1085 - 1100 .

MAHADEVAN U ， ROBINSON C ， BERNASKO N ， et al . Inflammatory bowel disease in pregnancy clinical care pathway：a report from the American Gastroenterological Association IBD Parenthood Project Working Group [J ] . Gastroenterology ， 2019 ， 156 （ 5 ）： 1508 - 1524 .

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