Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in young children and results in significant healthcare burden and costs. To reduce the impact of RSV in this population, the monoclonal antibody palivizumab has historically been used. Recently, new preventive options have become available, including a longer-acting monoclonal antibody (nirsevimab) and a maternal vaccine (RSVpreF). To compare the cost-effectiveness of various immunization strategies, we developed a discrete-event simulation model using epidemiological and cost data from British Columbia, along with published efficacy estimates. The model simulated a cohort of 100,000 newborns over two years. We conducted the analysis from a healthcare system perspective, projecting health outcomes (inpatient and outpatient visits), costs (in Canadian dollars), and quality-adjusted life years (QALYs) under five immunization strategies: (1) palivizumab for high-risk children (reference); (2) nirsevimab for high- and moderate-risk children; (3) in-season maternal RSVpreF vaccination combined with nirsevimab for high-risk children; (4) in-season maternal RSVpreF plus nirsevimab for moderate- and high-risk children; and (5) nirsevimab for all infants. We applied an incremental cost-effectiveness ratio (ICER) threshold of $50,000 per QALY as the willingness-to-pay benchmark for evaluating cost-effectiveness. Compared to strategy 1 (palivizumab), strategy 2 was dominant—improving health outcomes while yielding the greater cost savings. Strategy 3 was also cost saving but was weakly dominated by other options. Strategy 4 was cost-effective, with an ICER less than half the willingness-to-pay threshold. In contrast, strategy 5 was not cost-effective, with an ICER exceeding five times the benchmark value under current assumptions for nirsevimab efficacy and a unit price of $450. These findings support policy recommendations to prioritize a publicly funded seasonal maternal RSVpreF immunization program plus nirsevimab administration for high- and moderate-risk children, as a cost-effective approach for broader reduction in RSV-related healthcare burden in young children.

The authors have declared no competing interest.

This study did not receive any funding

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The Ministry of Health's Data Stewardship Committee of the Government of British Columbia approved access to the data used in this study. The University of British Columbia Clinical Research Ethics Board waived ethical approval for this work, as the analysis was conducted using de-identified administrative health data.

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