Impact and cost-effectiveness of the 6-month BPaLM regimen for rifampicin-resistant tuberculosis: a mathematical modeling analysis

Abstract

BackgroundEmerging evidence suggests that shortened, simplified treatment regimens for rifampicin-resistant tuberculosis (RR-TB) can achieve comparable end-of-treatment outcomes to longer regimens. We compared a 6-month regimen containing bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) to a standard of care strategy using a 9- or 18-month regimen depending on whether fluoroquinolone resistance (FQ-R) is detected on Drug Susceptibility Testing (DST).Methods and FindingsGenomic and associated demographic data were used to parameterize a mathematical model estimating long-term health outcomes and costs (2022 USD) for each treatment strategy for patients 15 years and older diagnosed with pulmonary RR-TB in Moldova, a country with a high burden of TB drug resistance. In this model individuals were followed over their lifetime, simulating the natural history of TB and associated treatment outcomes, as well as the process of acquiring resistance to each of 12 anti-TB drugs. Compared to the standard of care, 6 months of BPaLM was estimated to reduce lifetime costs by $3433 (95% Uncertainty Interval (UI): 1480, 5771) per individual, with a small non-significant reduction in quality adjusted life expectancy of 0.06 QALYs (95% UI: −0.33, 0.45). For those stopping moxifloxacin under the BPaLM regimen, continuing with BPaLC provided more QALYs at lower cost than continuing with BPaL alone. Such a regimen (6 months of BPaLM, where clofazimine is added in the event of moxifloxacin discontinuation) had a 92% chance of being cost-effective. With the exception of pretomanid and delamanid, 6 months of BPaLM either reduced or resulted in no significant change in the cumulative incidence of resistance to each drug. Sensitivity analyses showed 6 months of BPaLM to be cost-effective across a broad range of values for the relative effectiveness of the drug regimens and the proportion of the cohort with FQ-R.ConclusionsCompared to the standard of care, the implementation of short-course regimens like BPaLM could improve the cost-effectiveness of care for individuals diagnosed with RR-TB, particularly in settings where current long-course regimens are challenging to implement and afford. Further research may be warranted to explore the suitability of 6 months of BPaLM in specific national settings, including locations where DST capacity is limited.