Efficacy and safety of short vs. Standard long regimens for multidrug- resistant tuberculosis: a network meta-analysis

Drug-resistant tuberculosis (DR-TB) remains a critical health concern, particularly in high- burden regions like Indonesia. Shorter treatment regimens have been proposed to improve outcomes for multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB). This systematic review and Bayesian network meta-analysis aimed to evaluate the efficacy and safety of these shorter regimens. Using PRISMA-NMA guidelines, we systematically searched multiple databases, including PubMed, Cochrane, Scopus, WOAJ, and WOS, for studies published between 2014 to 2024. We included 23 eligible studies comprising a total of 6,343 MDR/RR- TB patients. Results showed that treatment with a 9-12 month regimen, specifically Kanamycin (Km)/Capreomycin (Cm), Moxifloxacin (Mfx)/Levofloxacin (Lfx), Prothionamide (Pto), Clofazimine (Cfz), Pyrazinamide (Z), Ethambutol (E), High-dose Isoniazid (Hh) demonstrated almost twice the probability of favorable outcomes defined as cure or treatment completion, compared to the standard regimens [RR 1.66 (95%CrI 1.34;2.04), P=0.0094]. Additionally, the 6-month regimen Bedaquiline (Bdq), Pretomanid (Pa), Linezolid (Lzd), Moxifloxacin (Mfx) also showed significantly higher favorable outcomes [RR 1.59 (95%CrI 1.29;2.03), P<0.001]. For safety outcomes, regimens containing bedaquiline, such as the 6-month Bdq, Pa, Lzd, Mfx regimen, had a 38% reduction in the risk of adverse events compared to the standard [RR 0.623 (95%CrI 0.280;1.29), P < 0.0001]. This was followed by the 6-month Bdq, Pa, Lzd and the Bdq, Pa, Lzd, Cfz regimen, which also showed lower risks of adverse events. In conclusion, shorter MDR/RR-TB regimens, especially those containing bedaquiline, appear to enhance cure rates while reducing adverse effects, supporting current WHO guidelines for 6-month treatment options