纳武利尤单抗相关免疫性心肌炎的文献病例分析  

Case Analysis of Immune-related Myocarditis Associated with Nivolumab based on Literature Reviews

作　　者：王东晓 种朝阳 古今 Wang Dongxiao;Chong Zhaoyang;Gu Jin(Department of Pharmacy,Peking University Shougang Hospital,Beijing 100144,China;Department of Clinical Pharmacy,the First Affiliated Hospital of Xi’an Medical College)

机构地区：[1]北京大学首钢医院药剂科,北京100144 [2]西安医学院第一附属医院临床药学室

出　　处：《药物流行病学杂志》2022年第5期346-352,共7页Chinese Journal of Pharmacoepidemiology

基　　金：首颐医疗科技发展基金项目(编号:SGYYZ202014)。

摘　　要：目的:分析纳武利尤单抗(Nivo)相关免疫性心肌炎的临床特点,为临床安全用药提供参考。方法:检索国内外文献数据库,收集Nivo相关免疫性心肌炎的文献病例报道,检索时限均为从建库至2021年6月,对患者基本信息、用药情况、Nivo相关免疫性心肌炎的临床特点等进行分析。结果:共纳入文献44篇/47例Nivo相关免疫性心肌炎患者,其中男28例,女19例;主要为黑色素瘤19例,肺癌10例,肾癌7例。32例发生在用药后2个月内。47例均存在心肌酶谱、心电图、超声心动图等异常,临床症状主要为喘憋、胸痛、心律失常等(37例次,34.26%);其次为肌无力、肌痛等(22例次,20.37%),疲劳、发热等(20例次,18.52%)。22例组织病理学诊断为免疫相关性心肌炎。45例接受激素及激素联合治疗。33例好转/恢复,14例死亡。1例无症状患者重启Nivo治疗。1例好转后重启帕博利珠单抗免疫治疗,再次发生免疫相关性心肌炎死亡。余患者均未再重启免疫治疗。结论:Nivo相关免疫性心肌炎临床表现多样、缺乏特异性、无特定预警因子,但致死率高。临床用药时应常规监测心脏生物标记物、心电图、超声心动图等,必要时CMR或心肌活检及早识别、治疗免疫相关性心肌炎,并谨慎重启免疫治疗。Objective:To analyze the clinical characteristics of immune-related myocarditis associated with nivolumab in order to provide reference for clinical safe drug use.Methods:PubMed,CNKI,WanFang Data and VIP databases were electronically searched to collect the cases of nivolumab-induced immune-related myocarditis published before June 2021,and then the data were analyzed statistically in terms of general information of patients,medication,clinical characteristics of nivolumab-induced immune-related myocarditis,etc.Results:A total of 44 literature/47 cases of nivolumab-induced immune-related myocarditis were enrolled in this study,among which 28 were male and 19 were female.19 cases were melanomains,10 cases were lung cancer and 7 cases were kidney cancer.32 cases developed nivolumab-induced immune-related myocarditis within 2 months of medication.All 47 cases had abnormal results of myocardial enzymogram,electrocardiogram and echocardiography,and the main clinical symptoms were dyspnea,chest pain and arrhythmia(37 times,34.26%)which were followed by muscle weakness and myalgia(22 times,20.37%),fatigue and fever(20 times,18.52%).22 cases were diagnosed with nivolumab-induced immune-related myocarditis by biopsy.45 cases were treated with glucocorticoid or glucocorticoid combination regime.33 cases improved/recovered and 14 died.One asymptomatic patient was restarted immunotherapy with nivolumab.One patient restarted immunotherapy with pembrolizumab after improvement and died due to recurring immune-related myocarditis.All the other cases did not restart immunotherapy.Conclusion:Immuno-related myocarditis associated with nivolumab has diverse and nonspecific clinical manifestations,no specific warning factors,but high mortality.Routine work-up should include cardiac biomarkers,an electrocardiogram,an echocardiography,probably a cardiac MRI and a cardiac biopsy in order to early recognize and deal with immuno-related myocarditis associated with nivolumab.And immunotherapy should be restarted carefully.

关 键 词：纳武利尤单抗 免疫相关性心肌炎 药品不良反应 文献病例分析 

分 类 号：R979.1[医药卫生—药品]