Interim Effectiveness and Safety of Prolonged Bedaquiline Use in Comparison to Standard 24-Week Treatment for MDR-TB: A Multicenter Cohort Study in China.

Purpose: Limited evidence exists regarding impacts of prolonged bedaquiline use in the treatment of multidrug-resistant (MDR) tuberculosis (TB). This study evaluated the effectiveness and safety of prolonged bedaquiline use (>24 weeks) compared to the standard 24-week in MDR/extensively drug-resistant (XDR)-TB treatment with longer regimen. Patients and Methods: This retrospective study analysed a prospective cohort of drug-resistant pulmonary TB patients treated with bedaquiline provided by the Global Drug Facility in China. Patients were enrolled from February 2018 to April 2020 across 21 hospitals under the New Drug Introduction and Protection Program. Prolonged use decisions were made by a central expert committee based on individual treatment responses. Effectiveness was assessed through cumulative culture conversion rates and time; safety was evaluated by monitoring adverse events (AEs). Results: Of 481 patients, 421 received standard bedaquiline treatment, and 60 received prolonged treatment. Median culture conversion time was 4 weeks in both groups (P = 0.443), with one patient in the prolonged group achieving culture conversion after 24 weeks. Rates of QT prolongation (30.0% vs 28.5%), deaths (0% vs 2.1%), and other AEs were comparable. During the first 24 weeks, the prolonged group had a lower AE rate overall (35.0% vs 51.3%), including serious AEs (1.7% vs 13.8%), grade >3 AEs (13.3% vs 30.4%), AEs leading to death (0% vs 2.1%), bedaquiline-related AEs (16.7% vs 26.6%), and AEs leading to bedaquiline discontinuation (0% vs 5.7%). Conclusion: Prolonged bedaquiline use is effective and well-tolerated without significantly increased toxicity, potentially benefitting bedaquiline-tolerant patients with positive sputum cultures after the standard 6-month treatment.