4款国产PD-1抑制剂不良反应文献回顾性分析

Retrospective analysis on adverse drug reactions of four PD-1 inhibitors reported in literature

目的:根据文献报道,分析4款国产程序性细胞死亡蛋白1(programmed cell death protein 1,PD-1)抑制剂不良反应的发生情况与临床特点,为临床安全用药提供参考。方法:检索PubMed、中国知网、万方等数据库,收集关于卡瑞利珠单抗、信迪利单抗、特瑞普利单抗和替雷利珠单抗4款PD-1抑制剂导致不良反应的个案报道进行分析。结果:检索到相关合格文献报道105篇,其中卡瑞利珠单抗42篇,共47例患者;信迪利单抗29篇,共30例患者;特瑞普利单抗21篇,共24例患者;替雷利珠单抗13篇,共15例患者。其中男性76例(65.5%),女性40例(34.5%),男女比例为1.9:1.0,年龄在29~84岁,发生时间主要在首次使用PD-1抑制剂后4个月内。免疫相关不良反应主要表现在皮肤及其附件毒性反应41例(34.5%)、内分泌系统不良反应25例(21.0%)、心血管系统不良反应22例(18.5%)。大多数患者经对症支持治疗后好转。结论:在接受4款国产PD-1抑制剂治疗的任何时间段都可能发生免疫相关不良反应(immune-related adverse effects,irAEs),其中皮肤系统不良反应发生率最高,其次是心血管和内分泌系统,提示临床在使用此类药物时,应严格控制适应证,结合患者病情和实际情况合理选择药物,在整个免疫治疗期间需密切监测,以减少或避免irAEs的发生,保障患者用药安全。

AIM:To analyze the occurrence and clinical characteristics of adverse drug reactions(ADR) induced by four programmed cell death protein 1(PD-1) inhibitors according to literature reports,and to provide reference for clinical safe medication.METHODS:PubMed,CNKI,and Wanfang,and other databases were searched to collect case reports of adverse reactions caused by four PD-1 inhibitors,including camrelizumab,sintilimab,toripalimab,and tislelizumab.RESULTS:A total of105 eligible literature reports were retrieved from the databases at home and abroad(as of June 1,2022),including 42 reports on camrelizumab with47 patients,29 reports on sintilimab with 30 patients,21 reports on toripalimab with 24 patients and 13 reports on tislelizumab with 15 patients.Among them,there were 76 males(65.5%) and 40females(34.5%),with a gender ratio of 1.9:1.0.The age range was between 29 to 84 years old,and the onset of ADR mainly occurred within 4 months after the first use of PD-1 inhibitors.Immune-related adverse reactions were mainly manifested as skin and its attachment(41 cases,34.5%),endocrine system(25 cases,21.0%),and cardiovascular system(22 cases,18.5%).Most patients improved after symptomatic and supportive treatment.CONCLUSION:Immune-related adverse effects(irAEs) may occur at any time during treatment with the four PD-1 inhibitors,among these the skin system is most frequently affected,followed by the cardiovascular and endocrine systems.This suggests the importance of individualized drug administration and stringent control over indications in clinical practice.Close monitoring throughout immunotherapy is essential to minimize or prevent irAEs,thus ensuring patient safety in medication usage.