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: The prospective 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 delamanid that may cause QT interval prolongation.
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χ2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。.