DRUG-RESISTANT tuberculosis (DR-TB) remains a formidable global public health challenge, undermining progress towards TB elimination. The recent development of potent new therapies has led to the emergence of shorter, all-oral treatment regimens that promise to transform outcomes for patients. A recent systematic review and meta-analysis synthesised the most current evidence from international clinical trials and observational studies, revealing that these innovative regimens are both highly effective and safer than traditional approaches.
The review included studies published between 2012 and February 2024, sourced from major databases including Medline and Scopus. Only clinical trials and cohort studies involving adults with DR-TB treated with bedaquiline (Bdq)-based regimens of up to 12 months were eligible. The primary outcomes were treatment success rate (TSR) and the incidence of serious adverse events (SAEs), compared against outcomes from longer regimens, both oral and injectable. Meta-analytic techniques were employed to pool treatment outcomes, and subgroup analyses were conducted to explore sources of variation.
A total of 12 studies comprising 1902 DR-TB patients from 11 countries were included in the analysis. The pooled treatment success rate for all-oral Bdq-based regimens was 83% (95% CI: 77%–89%), with mortality, treatment failure and loss to follow-up (LTFU) rates of 5%, 4% and 4%, respectively. There was no significant difference in TSR when stratified by TB resistance profile or HIV status. SAEs occurred in 19% of patients, with QTc interval prolongation reported in 5%. Compared to longer or injectable-based regimens, Bdq-based short-course therapy was associated with significantly improved success (relative risk [RR] 1.22; 95% CI: 1.04–1.43), and lower rates of mortality (RR 0.73; 95% CI: 0.69–0.99), failure (RR 0.33; 95% CI: 0.32–0.62), and QTc prolongation (RR 0.39; 95% CI: 0.21–0.73).
These findings provide robust evidence supporting the wider adoption of all-oral, shorter Bdq-based regimens in DR-TB treatment. The regimens not only yield better clinical outcomes but also reduce the burden of adverse effects and treatment duration, which may enhance adherence and accessibility. However, limitations include variation in study design and settings, and a reliance on pooled observational data. Nonetheless, the data strongly support a shift in clinical practice and policy towards expanding access to shorter, safer DR-TB treatments.
Reference
Fekadu G et al. Impact of all-oral bedaquiline-based shorter regimens in the treatment of drug-resistant tuberculosis: a systematic review and meta-analysis. BMJ Glob Health. 2025;DOI: 10.1136/bmjgh-2024-018220.
