Real-world data on combination treatment with bedaquiline in patients with multidrug-resistant pulmonary tuberculosis in Japan: an interim analysis of post-marketing surveillance.

Abstract

Background: An observational post-marketing surveillance (PMS) is being conducted to evaluate the long-term safety and effectiveness of bedaquiline as part of combination therapies in treating pulmonary multidrug-resistant tuberculosis (MDR-TB) in Japan.

Methods: This interim analysis includes patients with MDR-TB who started bedaquiline-containing anti-tuberculosis (TB) drugs in Japan between January 2018 and September 2022. Outcomes include the incidence of adverse drug reactions (ADRs) and negative sputum cultures.

Results: In total, 112 patients were included in the safety analysis. All patients were receiving anti-TB drugs in addition to bedaquiline at baseline; 96.4% were receiving ≥3 drugs. The most commonly used concomitant anti-TB drugs were delamanid, cycloserine, linezolid, and levofloxacin hydrate. At 24 weeks after bedaquiline initiation, in the effectiveness analysis set, 19/20 (95.0%) had negative sputum mycobacteria growth indicator tube cultures and 9/12 (75.0%) have negative solid medium cultures. Patients received bedaquiline for a median of 186.0 days, during which 85 ADRs occurred in 45 patients (40.2%). The top three ADRs were electrocardiogram QT prolonged (9.8%), nausea (7.1%), and hepatic function abnormal (4.5%).

Conclusions: This interim analysis of a PMS supports the long-term safety and effectiveness of bedaquiline for MDR-TB in Japan. ADRs were consistent with previous reports and no new safety signals were detected. The final analysis of this ongoing PMS will be expected to confirm these findings.