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

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) 〕 (PLzd (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) 〕 (PLzd (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.