Prolonged Bedaquiline Treatment for RR/MDR-TB Not Likely to Improve Outcomes

Use of bedaquiline (BDQ) for longer than 6 months did not improve the probability of treatment success in patients with multidrug-resistant tuberculosis, according to study findings published in the American Journal of Respiratory and Critical Care Medicine.

Although the World Health Organization recommends use of BDQ for at least 6 months for MDR-TB, evidence showing the effectiveness of this recommendation is lacking. Researchers therefore compared the effectiveness of 6 months of BDQ vs longer-term BDQ use (ie, 7-11 months or ≥12 months) on favorable end-of-treatment outcomes.

The current study used data from the endTB observational study of 2,789 patients with RR/MDR-TB from 17 countries treated according to WHO guidelines with an 18- to 24-month regimen including BDQ and/or delamanid. Investigators for the current study used data from endTB to conduct an analysis designed to emulate a proposed endTB target trial. The analysis included data from 1468 participants aged 10 to 78 years (median age, 34 years; 63.8% male) with RR/MDR-TB who received a median of 4 likely-effective drugs as part of their treatment, with 87.1% receiving linezolid, 77.7% receiving clofazimine, and 33.7% receiving a fluoroquinolone.

Using data from this cohort, the investigators estimated the probability of successful treatment of individuals with RR/MDR-TB who initiated BDQ within 1 month of treatment initiation, completed 24 weeks of BDQ within the initial 27 weeks of treatment, and had no previous exposure or evidence of resistance to BDQ at week 23. For the analysis, participants were randomly assigned to 1 of 3 cohorts with varying BDQ treatment durations (6 months, 7-11 months, or ≥12 months). The outcome of interest was successful treatment, which would include cure and treatment completion. A 3-step analysis procedure was used to compare outcomes for the 3 therapy durations.

In the baseline-adjusted analyses and inverse probability-weighted analyses, the predicted probability of successful treatment was 0.85 (95% CI, 0.81, 0.88) for 6 months of BDQ, 0.77 (95% CI, 0.73, 0.81) for 7 to 11 months, and 0.86 (95% CI, 0.83, 0.88) for treatment of 12 months or more.

Compared with 6 months of BDQ, the treatment success ratio was 0.91 (95% CI, 0.85, 0.96) for 7 to 11 months and 1.01 (95% CI, 0.96, 1.06) for at least 12 months of treatment. The unadjusted and age- and sex-adjusted analyses were more extreme compared with the adjusted estimates. The differences in treatment success were -0.08 (95% CI, -0.13, -0.03) for 7 to 11 months and 0.01 (95% CI, -0.03, 0.05) for at least 12 months.

A treatment success ratio of 1.09 (95% CI, 1.05, 1.14) for at least 12 months of BDQ compared with 6 months was observed in a baseline-adjusted analysis that accounted for immortal person time bias.

In citing the study limitations, the researchers noted that the estimated small decrease in probability of successful treatment for 7 to 11 months vs 6 months of BDQ may be explained by random variability or misclassification of treatment adherence. In addition, in the programmatic setting, TB treatment adherence data are generally reported by health workers from monthly treatment cards, which may overestimate adherence and lead to missing values (12%). Furthermore, the adherence data obtained were for overall treatment, and data specific to BDQ were lacking. The design of this study, which used observational data to emulate a randomized controlled trial and estimate treatment effects, is a further study limitation.

“Bedaquiline use beyond six months did not increase the probability of successful treatment among patients receiving longer regimens that commonly included new and repurposed drugs,” concluded the investigators. “Future analyses should focus on subgroups with advanced disease, extensively drug-resistant strains, and/or less potent regimens that could potentially benefit from longer durations.”

Disclosures: Bedaquiline donations made from Janssen to the Global Drug Facility were used for patients in the endTB observational study. Donations of delamanid from Otsuka were used for initial patients enrolled in the endTB observational study. Please see the original reference for a full list of disclosures.

This article originally appeared on Pulmonology Advisor