AIMS To evaluate the potential public health impact and cost-effectiveness of vaccination using mRNA-1345 administered as a single dose compared with no vaccination in Italian high-risk adults aged 60-74 years and all adults aged ≥75 years. METHODS A static decision-analytic model was developed to project clinical and economic outcomes over a five-year time horizon, assuming 50% vaccination coverage among eligible adults. Economic outcomes were evaluated from the Italian National Health Service (Servizio Sanitario Nazionale, SSN) perspective. Model inputs were informed by the most recent Italian epidemiological, clinical, and economic evidence, supplemented by published international data when necessary. Deterministic, probabilistic, and scenario analyses were conducted to assess the impact of uncertainty in model inputs and assumptions on the study results. RESULTS Vaccination with mRNA-1345 in high-risk adults aged 60-74 years and all adults aged ≥75 years was projected to avert over 19,800 hospitalizations, 4,000 emergency department visits, 381,000 outpatient visits, 6,000 RSV-attributable deaths, and 212,000 antibiotic prescriptions compared with no vaccination over a five-year period. The total incremental cost of €1,143 million and the additional 47,477 QALYs gained resulted in an ICER of €24,078 per QALY gained, which was below the commonly referenced willingness-to-pay range of €33,000-40,000/QALY. Sensitivity analyses confirmed robustness of the analysis results. LIMITATIONS Due to limited epidemiological evidence for Italy, selected epidemiological inputs were informed by studies conducted in other high-income countries. In addition, vaccine efficacy beyond the two-year clinical trial follow-up was projected to five years using nonlinear waning curves fitted to the observed trial data. CONCLUSIONS Vaccination with mRNA-1345 is a cost-effective strategy for the prevention of RSV in high-risk adults aged 60-74 years and all adults ≥75 years in Italy, in comparison to no vaccination, and has the potential to provide substantial public health benefits.
