Cost-effectiveness of BPaL-based and 9-month modified all-oral short treatment regimens for rifampicin-resistant tuberculosis in Belarus

Belarus remains a high-burden country for multidrug-/rifampicin-resistant tuberculosis (MDR/RR-TB), including pre-extensively drug-resistant TB (pre-XDR-TB). BPaL-based and modified 9-month short treatment regimens (mSTR), implemented under operational research conditions, have demonstrated improved clinical outcomes, but evidence on their cost-effectiveness in real-world settings remains limited. We evaluated the cost-effectiveness of BPaL-based regimens containing bedaquiline, pretomanid, and linezolid with either moxifloxacin or clofazimine (BPaL(M/C)); mSTR composed of bedaquiline, levofloxacin, linezolid, clofazimine, cycloserine, or delamanid; and standard of care (SOC; ≥ 18-month regimens) for MDR/RR-TB and pre-XDR-TB in Belarus over a 20-year horizon using a cohort-based Markov model. Clinical effectiveness, safety, and cost inputs were derived from operational research and WHO data. Health outcomes were measured in quality-adjusted life-years (QALYs), costs were expressed in 2022 USD, and both were discounted at 3% annually. Incremental costs, QALYs, and incremental net monetary benefits (INMB) were estimated. Univariate, probabilistic, and conservative scenario analyses were conducted. A scale-up analysis assessed national budgetary implications. Probabilistic sensitivity analysis showed that both shorter regimens were cost-effective compared with SOC at the Belarus-specific willingness-to-pay threshold, with mean [IQR] INMB of USD 27,586 [16,248; 37,645] for BPaL(M/C) and USD 23,488 [10,887; 35,092] for mSTR versus SOC. In the base case, BPaL(M/C) was the most cost-effective strategy, with lower mean costs (USD 8,155) and higher effectiveness (10.82 QALYs) than SOC (USD 20,757; 8.91 QALYs). mSTR was also cost-effective compared with SOC but less effective than BPaL(M/C). Results were robust across sensitivity and scenario analyses. Under conservative assumptions of identical clinical outcomes, shorter regimens remained cost-saving. The scale-up analysis showed that expanding use of shorter regimens in Belarus could generate annual TB programme budget savings exceeding USD 9.8 million. BPaL(M/C) and mSTR are cost-effective alternatives to SOC in Belarus, offering substantial economic benefits at both patient and programmatic levels.