基于WHO-VigiAccess的5种PD-1/PD-L1单抗不良反应特点分析

Characteristic Analysis of Adverse Reactions of Five PD-1/PD-L1 Anti-cancer Monoclonal Antibodies Based on WHO-VigiAccess

目的比较程序性细胞死亡蛋白受体1(PD-1)及其配体1(PD-L1)靶点的单抗抗癌药药品不良反应(ADR)的特点,为临床安全用药提供参考依据。方法提取世界卫生组织药品不良反应报告数据库(WHO-VigiAccess)中替雷利珠单抗、帕博利珠单抗、纳武利尤单抗、度伐利尤单抗和阿替利珠单抗自发ADR报告数据,时间截至2021年,对5种单抗ADR症状的报告比例、ADR的共同点和差异性进行比较。结果获得5个单抗ADR报告数共105004份。5个单抗的ADR常发生在胃肠系统疾病系统,至少有3个单抗的ADR常发生于呼吸系统、胸及纵隔疾病,感染及侵染类疾病和皮肤及皮下组织类疾病系统。度伐利尤单抗在呼吸系统、胸及纵隔疾病,阿替利珠单抗在各类神经系统疾病,纳武利尤单抗在内分泌系统,替雷利珠单抗在心脏器官疾病系统的ADR报告比例明显高于其他药品。5个单抗的常见ADR症状有腹泻、呕吐、恶心、感染性肺炎、呼吸困难。除替雷利珠单抗外,4个单抗还常见结肠炎、瘙痒、食欲下降、关节痛、咳嗽、甲状腺功能异常的症状。度伐利尤单抗发生肺部炎症和纳武利尤单抗发生2型糖尿病症状的情况尤为突出。纳武利尤单抗死亡案例报告比例最高。在多个单抗中出现低血压和心肌炎等新的ADR症状。结论5个PD-1/PD-L1单抗常见的ADR涉及疾病系统和具体症状基本与药品说明书一致,但也存在一些特异性的和新发的ADR症状。应依据PD-1/PD-L1单抗的ADR特点,提高合理用药水平。

Objective The characteristics of adverse drug reactions(ADRs)that occur globally after the marketing of monoclonal anticancer drugs targeted by programmed cell death protein receptor 1(PD-1)and its ligand 1(PD-L1)were compared,to provide a reference for clinical drug safety.Methods Extracting the spontaneous ADR reporting data of five anti-PD-1 or PD-L1 mAbs for cancer treatment including tislelizumab,pembrolizumab,nivolumab,durvalumab and atezolizumab from the WHO-VigiAccess as of December 31,2021 was carried out.ADR report proportions of these five mAbs and their similarities and differences were further found.Results A total of 105004 ADR reports of 5 PD-1/PD-L1 mAbs were obtained.The types of reported ADRs of the five mAbs mainly included gastrointestinal disorders,and at least three of them also occurred in respiratory,thoracic and mediastinal disorders,infections and infestations,and skin and subcutaneous tissue disorders.The ADR report ratios of durvalumab in respiratory,thoracic and mediastinal disorders,of tezolizumab in nervous system disorders,of nivolumab in endocrine disorders and of tislelizumab in cardiac disorders were significantly higher than the average value and those of other drugs.The common ADR symptoms of the five mAbs included diarrhea,vomiting,nausea,pneumonia and dyspnea.Four mAbs except tislelizumab had common ADRs including colitis,pruritus,decreased appetite,arthralgia,cough and thyroid disorder.Lung inflammation and symptoms of type II diabetes mellitus are particularly pronounced with durvalumab nivolumab,respectively.Nivolumab had the highest reported proportion of death.New ADRs such as hypotension and myocarditis occurred in several mAbs.Conclusion The disease systems and risk signals involved in the common ADRs of the five PD-1/PD-L1 mAbs were basically consistent with the drug instructions,but there were also some specific and new ADRs.According to the ADR characteristics of five PD-1/PD-L1 mAbs,clinical medical workers can promote the level of rational use of mAbs.