Economic Evaluation of PCV21 Use in Populations with Increasing Serotype 4 Invasive Pneumococcal Disease in the US: An Attributable Fraction Threshold Analysis

INTRODUCTION: The 21-valent pneumococcal conjugate vaccine (PCV21) covers 83-88% of IPD in US adults but does not include serotype 4 (ST4), which is covered by previously recommended vaccines (PPSV23, PCV15, PCV20). Recent increases in IPD cases due to ST4 have been observed, particularly among adults under 65, including Native American/Alaskan Native and those with social risk factors. As a result, the Advisory Committee on Immunization Practices (ACIP) recommends ST4-containing vaccines (PPSV23, PCV15, and PCV20) for populations with ≥ 30% ST4 IPD cases. In this study, we aimed to analyze ST4 attributable fraction (AF) thresholds for health and economic outcomes of PCV21 versus PCV20 vaccination in US adults aged 19-49 and 50-64 years with underlying medical conditions. METHODS: We used a validated Markov model to estimate incremental cost-effectiveness ratios (ICERs) for PCV21 versus PCV20 and identified ST4 AF thresholds in which the ICER shifted from 'cost-saving' to 'not cost-effective'. The analysis involved a hypothetical 1 million at-risk adults aged 19-49 and 50-64 years. RESULTS: PCV21 remained cost-saving compared to PCV20 when ST4 accounted for ≤ 27% (age 19-49) or ≤ 36% (age 50-64) of IPD. When ST4 increases were applied to both IPD and NBPP, these thresholds decreased to ≤ 21% and ≤ 28%, respectively. CONCLUSION: For populations experiencing moderate increases in the proportion of ST4 (i.e., < 30%), PCV21 may offer health and economic benefits over PCV20 for US adults aged 19-64 years with underlying medical conditions. However, in populations with ≥ 30% ST4, ST4-containing vaccines should be used as per ACIP guidance.