含德拉马尼方案治疗我国耐多药和利福平耐药肺结核患者的阶段性不良反应临床分析  

Clinical analysis of adverse reactions in patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis treated with delamanid-containing regimen

作　　者：高孟秋[1] 高静韬[2] 马晓格 舒薇[2] 杜鹃 梁瑞霞[5] 吴桂辉 裴异[7] 严晓峰[8] 蔡青山[9] 吕康言 蔡翠 吴于青[12] 李秀杰 刘群群[14] 金龙 仵倩红 熊瑜 李明武 周莹荃 邝浩斌[20] 王霞芳[21] 任斐 陈晓红 耿书军[24] 周勇 沙巍[26] 杨国立[27] 王华 占颖 刘宇红[2] 李亮[2] Gao Mengqiu;Gao Jingtao;Ma Xiaoge;Shu Wei;Du Juan;Liang Ruixia;Wu Guihui;Pei Yi;Yan Xiaofeng;Cai Qingshan;Lyu Kangyan;Cai Cui;Wu Yuqing;Li Xiujie;Liu Qunqun;Jin Long;Wu Qianhong;Xiong Yu;Li Mingwu;Zhou Yingquan;Kuang Haobin;Wang Xiafang;Ren Fei;Chen Xiaohong;Geng Shujun;Zhou Yong;Sha Wei;Yang Guoli;Wang Hua;Zhan Ying;Liu Yuhong;Li Liang(Department of Tuberculosis,Beijing Chest Hospital,Capital Medical University,Beijing 101149,China;Beijing Chest Hospital,Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute/Clinical Center on Tuberculosis,China CDC,Beijing 101149,China;Department of Epidemiology,School of Public Health,Cheeloo College of Medicine,Shandong University,Jinan 250012,China;TuberculosisⅣWard,Wuhan Pulmonary Hospital,Wuhan 430030,China;Department of Tuberculosis,Henan Chest Hospital,Zhengzhou 450008,China;Department of Tuberculosis,Chengdu Public Health Clinical Medical Center,Chengdu 610066,China;Department of Drug-resistant Tuberculosis,Changsha Central Hospital,Changsha 410028,China;Chongqing Public Health Medical Treatment Center,Chongqing 400030,China;Department of Tuberculosis,Hangzhou Red Cross Hospital,Hangzhou 310005,China;Department of Tuberculosis,Chest Hospital of Guangxi Zhuang Autonomus Region,Nanning 530116,China;Tuberculosis Quality Control Center,Guiyang Public Health Treatment Center,Guiyang 550001,China;Department of Tuberculosis,Jiangxi Chest Hospital,Nanchang 330008,China;Department of Tuberculosis,Jiamusi Tuberculosis Prevention and Control Hospital,Jiamusi 154007,China;Department of Drug-resistant Tuberculosis,Taiyuan Fourth People′s Hospital,Taiyuan 030053,China;Department of Tuberculosis Internal Medicine,Heilongjiang Provincial Infectious Disease Prevention and Treatment Hospital,Harbin 150599,China;Department of Tuberculosis Internal Medicine,Shaanxi Tuberculosis Prevention and Control Institute,Xi′an 710105,China;Department of Tuberculosis,Shandong Public Health Clinical Center,Jinan 250013,China;Department of Drug-resistant and Severe T

机构地区：[1]首都医科大学附属北京胸科医院结核二科,北京101149 [2]首都医科大学附属北京胸科医院,北京市结核病胸部肿瘤研究所,中国疾病预防控制中心结核病防治临床中心,北京101149 [3]山东大学齐鲁医学院公共卫生学院流行病学系,济南250012 [4]武汉市肺科医院结核IV病区,武汉430030 [5]河南省胸科医院结核内科,郑州450008 [6]成都市公共卫生临床医疗中心结核科,成都610066 [7]长沙市中心医院耐药结核科,长沙410028 [8]重庆市公共卫生医疗救治中心,重庆400030 [9]杭州市红十字会医院结核科,杭州310005 [10]广西壮族自治区胸科医院结核科,南宁530116 [11]贵阳市公共卫生救治中心结核病质控中心,贵阳550001 [12]江西省胸科医院结核科,南昌330008 [13]佳木斯市结核病防治院结核科,佳木斯1540007 [14]太原市第四人民医院耐药结核科,太原030053 [15]黑龙江省传染病防治院结核内科,哈尔滨150599 [16]陕西省结核病防治院结核内科,西安710105 [17]山东省公共卫生临床中心结核科,济南250013 [18]昆明市第三人民医院耐药与重症结核病科,昆明650041 [19]兰州市肺科医院感染科,兰州730030 [20]广州市胸科医院结核内科,广州510095 [21]苏州市第五人民医院肺科,苏州215505 [22]西安市胸科医院结核科,西安710018 [23]福州肺科医院结核科,福州350008 [24]河北省胸科医院结核科,石家庄050047 [25]武汉市金银潭医院呼吸科,武汉430048 [26]上海市肺科医院结核科,上海200433 [27]吉林省结核病医院耐药科,长春130062 [28]安徽省胸科医院结核科,合肥230022 [29]北京结核病诊疗技术创新联盟,北京101149

出　　处：《中华结核和呼吸杂志》2024年第7期638-646,共9页Chinese Journal of Tuberculosis and Respiratory Diseases

基　　金：北京市医院管理中心“登峰”人才培养计划(DFL20221401)。

摘　　要：目的探讨含德拉马尼方案治疗耐多药和利福平耐药肺结核(MDR/RR-PTB)患者24周治疗过程中药物不良反应发生的特点。方法前瞻性多中心研究。2020年6月至2023年6月,在全国26家结核病医疗机构纳入符合条件的MDR/RR-PTB患者608例,其中男364例,女244例,年龄39.6(19.0~68.0)岁。给予含德拉马尼的化疗方案进行治疗,全程密切督导患者服药,监测并记录治疗过程中发生的所有不良反应,通过描述性分析评价不良反应发生的临床特点,用χ^(2)检验及多因素logistic回归分析QTcF(采用Fridericia公式校正的QT值)间期延长的相关影响因素。结果纳入本研究的608例患者在24周治疗期间内共有325例(53.5%)报告了710例次不良反应。发生频率最高的前6位依次是血液系统损害(143例,23.5%)、心电图QT间期延长(114例,18.8%)、肝毒性(85例,14.0%)、胃肠道反应(41例,6.7%)、周围神经病(25例,4.1%)、精神障碍(21例,3.5%)。心电图QT间期延长大多发生在距首次服药的第12周,其中严重不良反应21例(3.5%)。精神障碍患者7例(1.2%),其中严重精神障碍者有2例(0.3%)。结论含德拉马尼方案阶段性治疗MDR/RR-PTB患者的安全性总体良好,不良反应发生率与国外研究相当。研究发现我国患者人群中QT间期延长的发生率高于国外的相关报道,提示在使用含德拉马尼等可能引起QT间期延长的药物时要加强心电图的监测。Objective To explore the characteristics of adverse drug reactions during the 24-week therapy with delamanid-containing regimen for patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis(MDR/RR-PTB).Methods Theprospective multicenter study was conducted from June 2020 to June 2023.A total of 608 eligible patients with MDR/RR-PTB were enrolled in 26 tuberculosis medical institutions in China including 364 males and 79 females,aged 39.6(19.0-68.0)years.Patients were treated with chemotherapy regimens containing delamanid.Patients were closely supervised during treatment of medication,and all adverse reactions occurring during treatment were monitored and recorded.The clinical characteristics of adverse reactions were evaluated by descriptive analysis.Chi-square test and multivariate logistic regression were used to analyze the related factors of QTcF interval prolongation(QT corrected with Fridericia's formula).Results Of the 608 patients enrolled in this study,325 patients(53.5%)reported 710 adverse events within 24 weeks of treatment.The top 6 most common complications were hematological abnormalities(143 patients,23.5%),QT prolongation(114 patients,18.8%),liver toxicity(85 patients,14.0%),gastrointestinal reaction(41 patients,6.7%),peripheral neuropathy(25 patients,4.1%)and mental disorders(21 patients,3.5%).The prolongation of QT interval mostly occurred in the 12th week after the first dose of medication.Serious adverse reactions occurred in 21 patients(3.5%).There were 7 patients(1.2%)with mental disorders,including 2 patients(0.3%)with severe mental disorders.Conclusions The safety of dalamanid-based regimen in the staged treatment of MDR/RR-PTB patients was generally good,and the incidence of adverse reactions was similar to that reported in foreign studies.This study found that the incidence of QT interval prolongation in Chinese patients was higher than that reported overseas,suggesting that the monitoring of electrocardiogram should be strengthened when using drugs containing d

关 键 词：结核 肺 结核 抗多种药物性 抗结核药 德拉马尼 不良反应 

分 类 号：R521[医药卫生—内科学]