1 Impact and cost-effectiveness of the 6-month BPaLM regimen for rifampicin-resistant tuberculosis: 1 a mathematical modeling analysis 2 3 July 28, 2023 4 5 Lyndon P. James, 1,2 Fayette Klaassen, 3 Sedona Sweeney, 4 Jennifer Furin, 5 Molly F. Franke, 5 Reza 6 Yaesoubi, 6 Dumitru Chesov, 7,8 Nelly Ciobanu, 9 Alexandru Codreanu, 9 Valeriu Crudu, 9 Ted Cohen, 10 7 Nicolas A. Menzies 2,3 8 9 Affiliations: 10 1. PhD Program in Health Policy, Harvard University, Cambridge, MA, USA 11 2. Center for Health Decision Science, Harvard T. H. Chan School of Public Health, Boston, MA, 12 USA 13 3. Department of Global Health and Population, Harvard T. H. Chan School of Public Health, 14 Boston, MA, USA 15 4. Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, 16 UK 17 5. Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA 18 6. Department of Health Policy and Management, Yale School of Public Health, New Haven, CT, 19 USA 20 7. Discipline of Pneumology and Allergology, Nicolae Testemitanu State University of Medicine 21 and Pharmacy, Chisinau, Moldova 22 8. Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany 23 9. Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova 24 10. Department of Epidemiology and Microbial Diseases, Yale School of Public Health, New Haven, 25 CT, USA 26 27 Corresponding author: LPJ 28 Corresponding author email: lyj519@mail.harvard.edu 29 30 ABSTRACT 31 32 Background: Emerging evidence suggests that shortened, simplified treatment regimens for rifampicin- 33 resistant tuberculosis (RR-TB) can achieve comparable end-of-treatment outcomes to longer regimens. 34 We compared a 6-month regimen containing bedaquiline, pretomanid, linezolid, and moxifloxacin 35 (BPaLM) to a standard of care strategy using a 9- or 18-month regimen depending on whether 36 fluoroquinolone resistance (FQ-R) is detected on Drug Susceptibility Testing (DST). 37 38 Methods and Findings: Genomic and associated demographic data were used to parameterize a 39 mathematical model estimating long-term health outcomes and costs (2022 USD) for each treatment 40 strategy for patients 15 years and older diagnosed with pulmonary RR-TB in Moldova, a country with a 41 high burden of TB drug resistance. In this model individuals were followed over their lifetime, simulating 42 the natural history of TB and associated treatment outcomes, as well as the process of acquiring resistance 43 to each of 12 anti-TB drugs. Compared to the standard of care, 6 months of BPaLM was estimated to 44 reduce lifetime costs by $3433 (95% Uncertainty Interval (UI): 1480, 5771) per individual, with a small 45 non-significant reduction in quality adjusted life expectancy of 0.06 QALYs (95% UI: -0.33, 0.45). For 46 those stopping moxifloxacin under the BPaLM regimen, continuing with BPaLC provided more QALYs 47 at lower cost than continuing with BPaL alone. Such a regimen (6 months of BPaLM, where clofazimine 48 is added in the event of moxifloxacin discontinuation) had a 92% chance of being cost-effective. With the 49 exception of pretomanid and delamanid, 6 months of BPaLM either reduced or resulted in no significant 50 change in the cumulative incidence of resistance to each drug. Sensitivity analyses showed 6 months of 51 . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 31, 2023. ; https://doi.org/10.1101/2023.07.28.23293104 doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.