Cost-effectiveness of Microbiota Restoration Therapies for Recurrent Clostridioides difficile Infection.

Abstract

BACKGROUND Recurrent Clostridioides difficile infection (rCDI) is associated with substantial morbidity, healthcare utilization, and costs. FDA-approved microbiota-based therapies, fecal microbiota spores, live-brpk (VOS) and fecal microbiota, live-jslm (RBL), reduce recurrence risk, but cost-effective placement within the rCDI treatment pathway remains uncertain. METHODS We performed a U.S. payer-perspective cost-effectiveness analysis using decision-tree modeling according to CHEERS 2022 guidelines. Adult with rCDI entered the model after the first or second recurrence and were followed for <1 year. Effectiveness inputs were derived from ECOSPOR III/IV (VOS), PUNCH CD3/CD3-OLS (RBL) trials, and published literature for standard-of-care (SoC) comparators. Outcomes included costs (2025 USD), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Probabilistic and deterministic sensitivity analyses were performed using a willingness-to-pay threshold of $150,000/QALY. ICERs were interpreted across $50,000, $100,000, $120,000, and $150,000/QALY. RESULTS After the first recurrence, RBL was cost-effective versus SoC alone ($25,415/QALY). Early initiation remained favorable compared with delayed use for VOS ($27,239/QALY) and RBL ($26,704/QALY). After the second recurrence, VOS remained cost-effective versus SoC (ICER $53,983/QALY), whereas RBL exceeded the willingness-to-pay threshold (ICER $171,496/QALY). Exploratory cross-trial VOS-versus-RBL comparisons yielded ICERs of $124,636/QALY after first recurrence and $137,350/QALY after second recurrence, indicating threshold-sensitive product-to-product comparisons. CONCLUSIONS Earlier initiation of microbiota-based therapies after the first CDI recurrence provides greater health benefits at acceptable cost-effectiveness thresholds compared with delayed use, supporting earlier integration into rCDI treatment strategies. VOS-versus-RBL comparisons should be interpreted as exploratory indirect comparisons pending comparative real-world or head-to-head data.