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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 Δ

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刘德凤 ，刘 蕊，钱 妍，杜青青（重庆医科大学附属第二医院药学部，重庆 400010）
中图分类号 R969.3；S859.79+ 文献标志码 A 文章编号 1001-0408（2024）12-1511-06
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。
关键词 炎症性肠病；生物制剂；英夫利昔单抗；阿达木单抗；乌司奴单抗；维得利珠单抗；不良事件

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（Dept. of Pharmacy， the Second Affiliated Hospital of
Chongqing Medical University， Chongqing 400010， China）

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.
KEYWORDS inflammatory bowel disease； biological agents； infliximab； adalimumab； ustekinumab； vedolizumab； adverse events

Δ 基金项目 重庆市自然科学基金面上项目（No.cstc2021jcyj- 炎症性肠病（inflammatory bowel disease，IBD）是一
msxmX0218） 组病因不明的慢性非特异性肠道炎症疾病，包括溃疡性
＊第一作者 主管药师，硕士。研究方向：临床药学。E-mail：
结肠炎（ulcerative colitis，UC）和克罗恩病（Crohn’s di-
183065649@qq.com
sease，CD），主要临床表现为反复发作的腹泻、腹痛、便
# 通信作者 副主任药师，硕士生导师，博士。研究方向：临床药
学。E-mail：Dorothydu@hospital.cqmu.edu.cn 血等，病程迁延不愈，易合并多种并发症，可增加结直肠

中国药房 2024年第35卷第12期 China Pharmacy 2024 Vol. 35 No. 12 · 1511 ·