中国药物警戒 ›› 2020, Vol. 17 ›› Issue (8): 480-486.
DOI: 10.19803/j.1672-8629.2020.08.07

• 安全与合理用药 • 上一篇    下一篇

免疫抑制剂Cemiplimab的药物毒性：基于FARES数据库的真实世界研究

胡方圆1, 叶小飞1, 翟映红1,2, 许金芳1, 郭晓晶1, 郭志坚1, 庄永龙3, 贺佳1,2,*   

  1. 1第二军医大学卫生勤务学系卫生统计学教研室,上海 200433;
    2同济大学医学院,上海 200092;
    3北京百奥知信息科技有限公司,北京 100098
  • 收稿日期:2020-07-31 修回日期:2020-07-31 出版日期:2020-08-15 发布日期:2020-07-31
  • 通讯作者: *贺佳,女,教授·博导,药物流行病学及新药评价。E-mail：hejia63@yeah.net
  • 作者简介:胡方圆,男,硕士,药物流行病学。

Drug-associated Toxicities of Cemiplimab: A Real-world Study Based on FARES Database

HU Fangyuan1, YE Xiaofei1, ZHAI Yinghong1,2, XU Jinfang1, GUO Xiaojing1, GUO Zhijian1, ZHUANG Yonglong3, HE Jia1,2,*   

  1. 1Department of Health Statistics, Second Military Medical University, Shanghai 200433, China;
    2Tongji University School of Medicine, Shanghai 200092, China;
    3Beijing Bioknow Information Technology Co.Ltd, Beijing 100098, China
  • Received:2020-07-31 Revised:2020-07-31 Online:2020-08-15 Published:2020-07-31
  • Supported by:
    国家科技重大专项（2017ZX09304030）：肿瘤和泌尿生殖系统疾病新药精准临床评价技术平台建设; 国家自然科学基金（81703296）：药品不良反应监测中多重性检验和低频数膨胀问题的研究; 上海市自然科学基金（18ZR1449500）：疾病风险评分模型研究及在药品不良反应主动监测中的应用; 上海市第四轮公共卫生三年行动计划重点学科建设项目循证公共卫生与卫生经济学(15GWZK0901); 上海市卫计委优秀青年医学人才培养计划（2018YQ47）

PDF (PC)

325

摘要： 目的 PD-1受体拮抗剂Cemiplimab为2018年最新获批的免疫抑制剂,已作为孤儿药用于转移性或局部晚期皮肤鳞状细胞癌患者的免疫治疗,但该药的药物毒性尚不明确。本研究旨在系统挖掘Cemipl-imab的潜在药物毒性,为后续临床免疫治疗提供借鉴。方法 数据来源美国FAERS数据库,采用不相称测定分析法中的报告比值法和信息成分法挖掘免疫抑制剂Cemiplimab的潜在药品不良事件信号,并采用MedDRA对FAERS数据库各不良事件名称进行标准化。结果 研究共纳入了10 051 679条记录,其中131条为Cemiplimab的药品不良事件记录。结果显示,Cemiplimab存在一定的药物毒性：乏力、背痛、血压下降、细胞因子释放综合征、肌肉痉挛、中性粒细胞减少症、肺栓塞、蜂窝织炎、肿瘤发炎、发热。多数Cem-iplimab相关的药品不良事件死亡、危及生命和残疾等严重结局所占的比例较高,需要引起警惕。结论 Cemiplimab存在一定的药物毒性,且多数Cemiplimab相关的药品不良事件的终点结局较差,临床免疫治疗时医疗人员应保持充分警惕,采取一定的预防措施,保证临床免疫治疗安全。

关键词: 免疫抑制剂, Cemiplimab, 药物毒性, FAERS数据库, 不相称测定分析法

Abstract: Objective To systematically characterize the potential drug toxicities of cemiplimab, a PD-1 inhibitor approved as an immune checkpoint inhibitor (ICI) in 2018 and used as an orphan drug for patients with metastatic or locally advanced cutaneous squamous cell carcinoma, in order to provide more evidence for subsequent ICIs immunotherapies. Methods Data was harvested from US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Disproportionality analysis involving the information component (IC) and reporting odds ratio (ROR) was used to detect potential association between cemiplimab and adverse events (AEs). MedDRA software was used to code data on adverse events in FAERS database into a standardized terminology. Results A total of 10 051 679 records were extracted from the database, with 131 of them for cemiplimab. It was shown that toxicities were detected in cemiplimab, which included asthenia, back pain, decreased blood pressure, cytokine release syndrome, muscle spasms, neutropenia, pulmonary embolism, cellulitis, tumour inflammation and pyrexia. The proportion of such severe outcomes as death, life-threating conditions and disability in most of these AEs was quite high, which deserves more attention. Conclusion Toxicities have been detected in cemiplimab, and most of the outcomes of cemiplimab-related AEs are undesirable. Thus, it is important for clinicians to be alert to AEs in cemiplimab immunotherapies and take measures to prevent the occurrence of AEs so as to ensure the safety of patients.

Key words: immune checkpoint inhibitors, cemiplimab, drug-associated toxicities, FAERS database, disproportionality analysis

中图分类号: