中国全科医学 ›› 2023, Vol. 26 ›› Issue (05): 598-606.DOI: 10.12114/j.issn.1007-9572.2022.0530

• 论著·医学循证 • 上一篇    下一篇

抗结核药物治疗耐多药结核病疗效和安全性的网状Meta分析

陈涛1,2, 范清泽1, 孙雪梅1, 喻永琪1,2, 罗宏丽1,*()   

  1. 1.646000 四川省泸州市,西南医科大学附属医院药学部
    2.646000 四川省泸州市,西南医科大学药学院
  • 收稿日期:2022-04-01 修回日期:2022-08-02 出版日期:2023-02-15 发布日期:2022-09-22
  • 通讯作者: 罗宏丽

  • 作者贡献:陈涛、范清泽、罗宏丽提出研究思路,制定检索策略;范清泽、罗宏丽负责文章的质量控制及审校;陈涛、孙雪梅查找文献,提取资料信息,进行统计学处理,撰写论文;陈涛、喻永琪进行资料/数据收集及整理;孙雪梅、喻永琪进行论文的修订;罗宏丽对文章整体负责,监督管理。

Efficacy and Safety of Anti-tuberculosis Drugs for the Treatment of Multidrug Resistance-tuberculosis: a Network Meta-analysis

CHEN Tao1,2, FAN Qingze1, SUN Xuemei1, YU Yongqi1,2, LUO Hongli1,*()   

  1. 1. Deptartment of Pharmacy, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
    2. School of Pharmacy, Southwest Medical University, Luzhou 646000, China
  • Received:2022-04-01 Revised:2022-08-02 Published:2023-02-15 Online:2022-09-22
  • Contact: LUO Hongli

摘要: 背景 二线抗结核药物在临床上广泛运用于耐多药结核病(MDR-TB),目前有多篇网状Meta分析对其进行研究,但治疗效果并不是令人十分满意。 目的 系统评价5种抗结核药物化疗方案治疗MDR-TB的疗效和安全性。 方法 计算机检索PubMed、Medline、Web of Science、维普网和万方数据知识服务平台关于抗结核药物化疗方案治疗MDR-TB的随机对照试验(RCT),检索时限为2010年1月至2022年3月。试验组采用个体化治疗方案分别联用莫西沙星(Mfx)、左氧氟沙星(Lfx)、利奈唑胺(Lzd)、氯法齐明(Cfz)、贝达喹啉(Bdq),对照组采用个体化治疗方案分别联用安慰剂、Lfx。筛选文献并提取数据后,运用Cochrane系统评价员手册5.1.0提供的偏倚风险评估工具进行质量评价;采用GeMTC 0.14.3软件和StataSE 15.0软件对痰培养转阴率、临床有效率、不良反应发生率进行贝叶斯网状Meta分析。 结果 共纳入39项RCT,共计3 860例患者。网状Meta分析结果显示,Bdq、Cfz、Lfx、Lzd、Mfx的痰培养转阴率均高于安慰剂〔OR=3.49,95%CI(2.11,5.73);OR=2.85,95%CI(1.93,4.23);OR=2.93,95%CI(1.45,6.94);OR=6.37,95%CI(3.67,11.31);OR=8.15,95%CI(3.97,18.47)〕(P<0.05),Cfz和Lfx的痰培养转阴率低于Mfx〔OR=0.34,95%CI(0.14,0.80);OR=0.36,95%CI(0.24,0.55)〕(P<0.05),Cfz的痰培养转阴率低于Lzd〔OR=0.44,95%CI(0.23,0.91)〕(P<0.05),累积排序概率曲线下面积(SUCRA)排序显示:Mfx(94.3%)>Lzd(82.1%)>Bdq(50.2%)>Lfx(37.5%)>Cfz(35.9%)>安慰剂(0.1%)。Bdq、Cfz、Lfx、Lzd、Mfx的临床有效率均高于安慰剂〔OR=2.80,95%CI(1.74,4.46);OR=2.02,95%CI(1.33,3.08);OR=4.93,95%CI(2.13,11.50);OR=5.72,95%CI(3.44,10.08);OR=3.20,95%CI(1.16,9.21)〕(P<0.05),Bdq、Cfz和Lfx的临床有效率低于Mfx〔OR=0.27,95%CI(0.08,0.77);OR=0.19,95%CI(0.07,0.53);OR=0.47,95%CI(0.29,0.74)〕(P<0.05),Bdq和Cfz的临床有效率低于Lzd〔OR=0.49,95%CI(0.23,0.97);OR=0.35,95%CI(0.17,0.68)〕(P<0.05),SUCRA排序显示:Mfx(87.4%)>Lzd(86.2%)>Lfx(54.6%)>Bdq(47.3%)>Cfz(24.3%)>安慰剂(0.1%)。5种抗结核药物与安慰剂不良反应发生率比较,差异均无统计学意义(P>0.05);各抗结核药物不良反应发生率组间比较,差异无统计学意义(P>0.05)。 结论 当前证据表明,Mfx和Lzd治疗MDR-TB相对于其他药物的疗效更优,因纳入研究与样本量较少,研究结果还需进一步验证。

关键词: 结核, 抗多种药物性, 莫西沙星, 左氧氟沙星, 利奈唑胺, 氯法齐明, 贝达喹啉, 网状Meta分析

Abstract:

Background

Second-line anti-tuberculosis drugs are widely used in clinic for multi-drug resistant tuberculosis (MDR-TB) . At present, there are several reticulated meta-analyses investigating them, but the effect is not very satisfactory.

Objective

To systematically evaluate the efficacy and safety of five anti-tuberculosis chemotherapy regimens in the treatment of MDR-TB.

Methods

Randomized controlled trials (RCTs) on anti-tuberculosis drug for MDR-TB were retrieved from PubMed, Medline, Web of Science, VIP, and Wanfang data from January 2010 to March 2022. The experimental group was treated with individualized treatment combined with moxifloxacin (Mfx) , levofloxacin (Lfx) , linezolid (Lzd) , clofazimine (Cfz) and bedaquiline (Bdq) . The control group was treated with individualized treatment combined with placebo or Lfx. After literature screening and data extraction, quality assessment was performed using the risk of bias assessment tool provided by the Cochrane system evaluator handbook 5.1.0. Bayesian network Meta-analysis on the rate of sputum culture conversion, clinical efficacy rate and incidence of adverse reactions was conducted using GeMTC 0.14.3 software and Stata SE 15.0 software.

Results

A total of 39 RCTs and 3 860 patients were included. Results of Meta-analysis showed that the rate of sputum culture conversion of Bdq, Cfz, Lfx, Lzd, Mfx, were higher than those of placebo〔OR=3.49, 95%CI (2.11, 5.73) ; OR=2.85, 95%CI (1.93, 4.23) ; OR=2.93, 95%CI (1.45, 6.94) ; OR=6.37, 95%CI (3.67, 11.31) ; OR=8.15, 95%CI (3.97, 18.47) 〕 (P<0.05) . The rate of sputum culture conversion of Cfz and Lfx was lower than Mfx〔OR=0.34, 95%CI (0.14, 0.80) ; OR=0.36, 95%CI (0.24, 0.55) 〕 (P<0.05) , and Cfz was lower than Lzd〔OR=0.44, 95%CI (0.23, 0.91) 〕 (P<0.05) in rate of sputum culture conversion. The surface under the cumulative ranking curve area (SUCRA) ranking showed the following: Mfx (94.3%) >Lzd (82.1%) >Bdq (50.2%) >Lfx (37.5%) >Cfz (35.9%) >placebo (0.1%) . The clinical response rates for Bdq, Cfz, Lfx, Lzd and Mfx were all higher than that of placebo〔OR=2.80, 95%CI (1.74, 4.46) ; OR=2.02, 95%CI (1.33, 3.08) ; OR=4. 93, 95%CI (2.13, 11.50) ; OR=5.72, 95%CI (3.44, 10.08) ; OR=3.20, 95%CI (1.16, 9.21) 〕 (P<0.05) , and Bdq, Cfz, and Lfx had lower clinical response rates than Mfx〔OR=0.27, 95%CI (0.08, 0.77) ; OR=0.19, 95%CI (0.07, 0.53) ; OR=0.47, 95%CI (0.29, 0.74) 〕 (P<0.05) , and lower clinical response rates for Bdq and Cfz than Lzd〔OR=0.49, 95%CI (0.23, 0.97) ; OR=0.35, 95%CI (0.17, 0.68) 〕 (P<0.05) , and the SUCRA ranking showed the following: Mfx (87.4%) >Lzd (86.2%) >Lfx (54.6%) >Bdq (47.3%) >Cfz (24.3%) >placebo (0.1%) . There were no significant differences both in the incidence of adverse reactions among the 5 anti-tuberculosis drugs and placebo (P>0.05) and in the incidence of adverse reactions of each anti-tuberculosis drugs between groups (P>0.05) .

Conclusion

Current evidence suggests that Mfx and Lzd are more effective than other drugs in the treatment of MDR-TB. The results of the study need to be further verified due to the small number clinical studies and sample size.

Key words: Tuberculosis, multidrug-resistant, Moxifloxacin, Levofloxacin, Linezolid, Clofazimine, Bedaquiline, Network meta-analysis