Cost-effectiveness of 20-valent versus 15-valent pneumococcal conjugate vaccines for infants in the Netherlands, taking into account indirect effects and adult vaccination

The 20-valent pneumococcal conjugate vaccine (PCV20) is approved for EU infants in a 3 + 1 schedule. In the Netherlands, PCV15 (2 + 1) was recently introduced into the national immunization program for infants, while a PCV20 program for older adults is being implemented. We evaluated the cost-effectiveness of replacing PCV15 (2 + 1) with PCV20 (3 + 1) for Dutch infants, taking into account indirect effects and their impact on the adult PCV20 program. A static, population-based Markov model estimated societal costs and quality-adjusted life-year (QALY) losses due to invasive pneumococcal disease and hospitalized non-invasive pneumococcal pneumonia in the Netherlands over a 10-year time horizon. Disease rates were based on a mature PCV10 infant program, with projections made for implementing PCV15 or PCV20, extrapolating magnitudes of indirect protection and serotype replacement from prior PCV13 programs. Among adults ≥ 60 years, PCV20 uptake was 55–70%, depending on age, with a scenario analysis exploring PCV21. Dutch vaccine list prices were applied. Replacing PCV15 (2 + 1) with PCV20 (3 + 1) in infants yielded QALY gains for children and adults aged < 60 years. However, among adults aged ≥ 60 years, early QALY gains were offset by later losses as indirect effects shifted disease to non-PCV20 serotypes, reducing the benefits of the adult PCV20 program. Over 10 years, this resulted in a net population-level loss of 3476 QALYs and €192 million in additional costs, making PCV15 (2 + 1) the dominant strategy. No net QALY loss was found when comparing PCV20 (3 + 1) with PCV15 (3 + 1) alongside an adult PCV21 program, as PCV21 includes eleven non-PCV20 serotypes. However, the incremental cost-effectiveness ratio was €304,781/QALY gained, well above conventional Dutch thresholds of €20,000–€50,000/QALY gained. Results were sensitive to magnitudes of indirect effects, time horizon, and vaccination costs of PCV20 versus PCV15. Replacing PCV15 (2 + 1) with PCV20 (3 + 1) for Dutch infants likely results in a net population-level health loss over 10 years when paired with a PCV20 program for older adults. If compared alongside an adult PCV21 program, no net health loss was found, but PCV20 (3 + 1) was not cost-effective at current list prices. Considering adult vaccination programs is essential when evaluating infant PCV strategies.