含贝达喹啉方案治疗耐多药/广泛耐药肺结核的24周不良反应临床分析

Clinical Analysis of Adverse Drug Reaction of Bedaquinoline-containing Regimens for the Treatment of Multidrug-resistant Tuberculosis or Extensively Drug-resistant Tuberculosis at 24 Weeks

目的探讨含贝达喹啉(Bdq)方案治疗耐多药(multidrug-resistant tuberculosis,MDR-TB)/广泛耐药肺结核(extensively drug-resistant tuberculosis,XDR-TB)患者24周治疗过程中药品不良反应(ADR)发生的特点,为Bdq的临床安全合理用药提供依据。方法以2019年3月—2020年3月安徽省胸科医院收治的“抗结核新药使用和保护扩展项目”的59例患者作为研究对象,给予含Bdq的耐药结核病化疗方案,全程密切督导患者治疗,收集并记录每例患者治疗过程中24周发生的所有ADR,通过描述性分析评价含Bdq方案ADR发生的特点。该研究仅为Bdq服药期间24周ADR的阶段性分析,患者尚未完成全部疗程。结果59例患者24周随访全部到位,无死亡病例,无失访病例或退组病例;59例患者ADR发生率为94.92%(56/59),共报告了ADR 156例次;其中属于轻度80.77%(级别1~2),属于严重19.23%(级别3~5)。治疗期间最常见的ADR是QT间期延长(18.59%)和血液系统损害(18.59%),肝脏毒性(14.10%)、外周神经炎(11.54%)、胃肠道反应(8.97%)、肾脏毒性(7.05%)、电解质紊乱(7.05%)也是较为常见的ADR。59例患者各监测时间的QTcF(采用Fridericia公式计算的QT值)平均值与基线平均值比较均增加,2,8,12,16,20,24周差异均有统计学意义,24周内未有患者QTcF值≥500 ms而导致停药,未有患者出现严重室性心律失常。结论应用含Bdq方案治疗MDR/XDR-TB,ADR发生率高,发生次数多,ADR表现多,但是在全程密切督导的管理模式下,疗效显著,严重ADR相对较少,未发现新的ADR,安全问题总体可控,患者的耐受性和依从性较好,方案值得进一步推广。

Objective To explore the characteristics of adverse drug reaction(ADR)in multidrug-resistant tuberculosis(MDR-TB)or extensively drug-resistant tuberculosis(XDR-TB)patients with Bedaquiline(Bdq)regimens during 24 weeks'treatment.The results provide evidence for clinical-safe use and monitoring of the drug Bdq.Methods Fifty-nine eligible patients from the“New Drug Introduction and Protection Program(NDIP)”were enrolled from March 2019 to March 2020 in Anhui Chest Hospitals.The patients were provided with chemotherapy regimens containing Bdq for drug-resistant tuberculosis.Close supervision was given to patients throughout the treatment process,and all ADRs that occurred during the treatment(24 weeks)on each patient was collected and recorded.A descriptive analysis evaluated the characteristics of ADRs in the Bdq regimen.This study was a only a phased analysis of ADR during Bdq administration(24 weeks),and most patients had not completed the full course of treatment.Results All fifty-nine patients were followed up for twenty-four weeks,and there was no death,no missing cases,and no withdrawal records from the group.The incidence rate of ADR was 94.92%(56/59),and 156 cases of ADR were reported.Among them,80.77%belonged to mild grade(grade 1—2),and 19.23%belonged to severe grade(grade 3—5).During treatment,the most common ADRs were prolonged QT interval(18.59%)and blood system damage(18.59%).And hepatotoxicity(14.10%),peripheral neuritis(11.54%),gastrointestinal reaction(8.97%),renal toxicity(7.05%),and electrolyte disorder(7.05%)were also common ADRs.The mean value of QTcF of 59 patients at each monitoring time was compared with the baseline mean value,and the difference was statistically significant except 4 weeps.Within 24 weeks,no patient's QTcF value≥500ms led to drug withdrawal,and no patient developed serious ventricular arrhythmia.Conclusion The application of Bdq regimen in the treatment of MDR/XDR-TB showed high incidence and frequent occurrence of ADRs.However,the serious ADRs was relatively few,and no new ADR was found under the management mode of close supervision throughout the whole process.The safety problems are generally controllable,and the patients have good tolerance and compliance.And the therapeutic effect is significant,so the treatment deserves a further promotion.