A Short, All-Oral Regimen for Pre-Extensively Drug-Resistant Tuberculosis: A Multicenter Open-label Single-arm Study.

Background: Pre-extensively drug-resistant tuberculosis (pre-XDR-TB) remains a critical public health threat due to limited treatment options and significant disease burden. Existing regimens have shown high success rates but are often inaccessible globally, necessitating alternative options.

Methods: This study was an open-label, multicenter, single-arm study conducted in China to evaluate the efficacy and safety of a 6- to 9-month oral regimen. Eligible participants, aged 18-70 with pulmonary pre-XDR-TB received a regimen of bedaquiline, linezolid, cycloserine, pyrazinamide and/or clofazimine. Pyrazinamide was either replaced with clofazimine or retained without clofazimine based on molecular susceptibility results. The primary efficacy endpoint was the percentage of participants with a favorable outcome at 84 weeks after treatment initiation in the modified intention-to-treat population.

Results: A total of 89 patients with pre-XDR-TB were enrolled. At 84 weeks after treatment initiation in the modified intention-to-treat analysis, 62 of 80 participants (77.5%; 95% confidence interval, 67.2% to 85.3%) had favorable outcomes. The 18 unfavorable outcomes were 5 regimen discontinuations or changes (6.3%, 4 due to adverse events and 1 decided by the local investigator), 4 bacteriological failures (5.0%), 4 withdrawals of consent (5.0%), 3 deaths (3.8%), and 2 losses to follow-up (2.5%). No relapse was reported after the end of treatment. Adverse events of grade 3 or higher were observed in 59.1% of participants, with QTc prolongation being the most frequently reported.

Conclusions: This study demonstrated that an all-oral, bedaquiline-based regimen provides a viable treatment option for patients with pre-XDR-TB, achieving acceptable efficacy and manageable safety profiles.