A Short, All-oral Regimen for Preextensively Drug-resistant Tuberculosis: A Multicenter Open-label Single-arm Study

Abstract Background Preextensively drug-resistant tuberculosis (pre-XDR-TB) remains a critical public health threat because of 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 years 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, 67.2–85.3) 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.