Real-world effectiveness of sequential pneumococcal vaccination in older adults: a cohort study.

Abstract

While real-world effectiveness of various pneumococcal vaccine formulations has been individually evaluated, comparative evaluations of PCV-13/PPSV-23/combinations thereof are limited. We evaluated real-world vaccine-effectiveness of PCV-13 alone, PPSV-23 alone, or PCV-13 followed by PPSV-23, in a population-based study of older adults. Population-based retrospective cohort study, including all adult Singaporeans aged≥65-89 years from 1st January 2020-31st July 2024. Time-to-event from cohort enrolment to pneumococcal-related-disease and all-cause pneumonia was measured, considering death as a competing risk event. Cox regression models were used to estimate cause-specific hazards, with PCV-13 alone/PPSV-23 alone/PCV-13 followed by PPSV-23 incorporated into models as time-dependent covariates together with patient demographics/comorbidities. Vaccination status was assessed using the National-Immunisation-Registry; outcomes were identified using national healthcare-claims data. 656,337 older Singaporeans were included; 348,831 (53.1%) remained unvaccinated by study end-date. Sequential PCV-13 followed by PPSV-23 significantly protected against pneumococcal-related disease (adjusted-hazards-ratio, aHR=0.22[95%CI=0.06-0.76]), pneumonia hospitalisations (aHR=0.94[95%CI=0.91-0.97]), and all-cause mortality (aHR=0.70[95%CI=0.67-0.74]). While PCV-13-alone also reduced risk of pneumonia hospitalisation (aHR=0.96[95%CI=0.92-0.99]) and all-cause mortality (aHR=0.86[95%CI=0.83-0.89]), vaccine-effectiveness estimates were numerically lower compared to sequential vaccination. For sequential vaccination, no significant waning of protection against all-cause pneumonia hospitalisation/mortality was observed; longer time-interval (≥365 days) between PCV-13 and PPSV-23 was associated with numerically lower risk of all-cause pneumonia hospitalisation/mortality, versus <365 days. In this population-based cohort study, PCV-13 followed by PPSV-23 was associated with lower risk of pneumococcal-related-disease, pneumonia and all-cause mortality; supporting recommendations for sequential vaccination in older adults.