Nirsevimab for RSV Prophylaxis in All Infants: Effectiveness, Cost-Effectiveness, and Equity Impact of Universal Versus Risk-Based Immunization in the First Year of Life

This study investigates real-world effectiveness, cost-effectiveness, and equity impact of universal nirsevimab RSV prophylaxis compared to risk-based (premature/CHD) immunization in infants during the 2024-2025 RSV season within the context of pediatric infectious disease and health technology assessment, an area of growing scientific importance given its implications for universal infant RSV prophylaxis policy design, VFC program inclusion, and equity-informed immunization program evaluation methodology. Using target trial emulation with propensity-score matched cohort analysis of RSV hospitalization, ED visit, LRTI diagnosis, and total healthcare cost within 6 months; ICER from payer and societal perspectives; equity analysis by insurance type and neighborhood income quintile, we examine nirsevimab monoclonal antibody against RSV F protein providing passive immunity for 5-6 months in infants who lack adaptive immunity, preventing viral replication and lower respiratory tract invasion that causes severe bronchiolitis requiring hospitalization in 12,840 nirsevimab-exposed infants (8 health systems, universal program) and 8,420 propensity-score matched unexposed controls from contemporaneous 2023-2024 season; 21,260 total; 6-month follow-up drawn from 8 U.S. children's hospital networks in 6 states with universal nirsevimab purchasing programs for 2024-2025 season; comparison to matched 2023-2024 unexposed cohort from same institutions. Results indicate that nirsevimab effectiveness 72.4% (95% CI 64.8-78.8%) vs. RSV hospitalization; universal program eliminates insurance-based equity gap (Medicaid vs. commercial OR 1.08, p=0.48 vs. 1.68 prior season, p<0.001); ICER $42,400/QALY (below $50k threshold) from payer perspective (p < 0.001), with 72.4% effectiveness; equity gap eliminated (OR 1.08 vs. 1.68); ICER $42,400/QALY as the primary quantitative benchmark. Concordance between primary and confirmatory measurement approaches exceeded 93%, validating the analytical framework. These findings contribute empirically to pediatric infectious disease and health technology assessment and carry actionable implications for the design of programs and policies targeting universal infant RSV prophylaxis policy design, VFC program inclusion, and equity-informed immunization program evaluation methodology.