中国药物警戒 ›› 2022, Vol. 19 ›› Issue (10): 1107-1112.
DOI: 10.19803/j.1672-8629.20210124

• 安全与合理用药 • 上一篇    下一篇

肿瘤免疫治疗药物程序性死亡分子/程序性死亡配体抑制剂的不良反应挖掘及评价

陈爽1,2,3, 郑淑芬2,4, 张述耀3, 钟诗龙1,2,4,*   

  1. 1汕头大学医学院药理学教研室,广东 汕头 515000;
    2广东省人民医院药学部,广东省医学科学院,广东 广州 510080;
    3暨南大学附属广州红十字会医院药学部,广东 广州510000;
    4南方医科大学药学院,广东 广州 510515
  • 收稿日期:2021-02-26 出版日期:2022-10-15 发布日期:2022-10-17
  • 通讯作者: *钟诗龙,男,博士,研究员·博导,临床药理。E-mail：zhongsl@hotmail.com
  • 作者简介:陈爽,女,在读硕士,临床药理。
  • 基金资助:
    2020年广东省科技专项资金项目[汕府科（2020）53号-20200602]

Adverse reactions of tumor immunotherapy drugs—PD-1/PD-L1 inhibitors

CHEN Shuang1,2,3, ZHENG Shufen2,4, ZHANG Shuyao3, ZHONG Shilong1,2,4,*   

  1. 1Department of Pharmacology, Shantou University Medical College, Shantou Guangdong 515000, China;
    2Department of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou Guangdong 510080, China;
    3Department of Pharmacy, Guangzhou Red Cross Hospital, Jinan University, Guangzhou Guangdong 510000, China;
    4School of Pharmaceutical Sciences, Southern Medical University, Guangzhou Guangdong 510515, China
  • Received:2021-02-26 Online:2022-10-15 Published:2022-10-17

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摘要： 目的 横向比对4种国内上市的进口免疫检查点抑制剂（ICI）—PD-1/PD-L1抑制剂药品不良反应（ADR）,并纵向比对其上市前后ADR,为临床合理安全使用ICI提供参考。方法 通过美国食品药品监督管理局（FDA）不良事件报告系统（FAERS）和OpenVigil平台对2013年1月21日至2020年9月30日的PD-1/PD-L1抑制剂ADR上报数据清洗与汇总,通过报告比值比（ROR）法进行ADR信号的筛选、统计和比对。结果 共获得44 220份ADR（纳武利尤单抗27 773份,帕博利珠单抗12 424份,阿特珠单抗2 875份,度伐利尤单抗1 148份）。根据系统-器官分类法（SOC）,ADR信号涉及的覆盖范围较大。ADR多为免疫相关不良反应（irAE）,常见为结肠炎、肺炎、肝功能异常和内分泌疾病的甲亢和Ⅰ型糖尿病;深层次挖掘出说明书未提及的其他ADR,包括胆管炎、肌炎、心肌炎、关节炎、神经疾病（如脑梗死）、脑水肿等。结论 进一步完善了PD-1/PD-L1抑制剂ADR信息,其ADR多为irAE,涉及全身多个系统-器官,严重时易危及患者生命。建议临床优化用药方案,减少患者治疗成本和ADR的发生。

关键词: PD-1/PD-L1抑制剂, 药品不良反应, 免疫治疗, 免疫相关不良反应

Abstract: Objective To provide data for rational and safe use of ICI in clinical practice via a comparison of the adverse drug reactions (ADR) caused by four types of PD-1/PD-L1 inhibitors, whose imported immune checkpoint inhibitors (ICI) are marketed in China. Methods The data on PD-1/PD-L1 inhibitors collected between January 21, 2013 and September 30, 2020 was cleaned and summarized by the FDA Adverse Event Reporting System (FAERS) and OpenVigil platform. Signals of ADR were screened, counted and compared using the report odds ratio (ROR). Results A total of 44 220 ADR cases were reported (27 773 cases related to nivolumab, 12 424 cases to pembrolizumab, 2 875 cases to atezolizumab, and 1 148 cases to durvalumab). The ADR covered a wide range according to the system organ classification (SOC). Most of those ADR were immune-related adverse events (irAE), such as colitis, pneumonia, liver dysfunction, hyperthyroidism and type I diabetes. Deeper mining exposed other ADR that were not mentioned in the instructions, including cholangitis, muscle Inflammation, myocarditis, arthritis, neurological diseases (such as cerebral infarction), and cerebral edema. Conclusion The information about ADR of PD-1/PD-L1 has been updated. Most of these ADR are irAE, involving multiple organs and systems of the body, which could be fatal in some cases. It is recommended that medication regimens be optimized to reduce the health care cost and ADR.

Key words: PD-1/PD-L1 inhibitor, adverse drug reaction, immunotherapy, immune-related adverse events (irAE)

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