Real-world effectiveness of 20-valent pneumococcal conjugate vaccine against all-cause outcomes among Medicare beneficiaries aged 65 years and older in the USA: a retrospective cohort study

Abstract

Background: The 20-valent pneumococcal conjugate vaccine (PCV20) was licensed for adults by the US Food and Drug Administration in 2021 on the basis of immunological criteria; however, vaccine effectiveness has not previously been reported. This study aimed to assess PCV20 vaccine effectiveness against invasive pneumococcal disease due to any serotype (all invasive pneumococcal disease), pneumococcal pneumonia due to any serotype (all pneumococcal pneumonia), all-cause pneumonia, and lower respiratory tract infections (LRTIs) and to estimate associated absolute rate reductions among adults aged 65 years and older in the USA. Methods: This retrospective, Medicare database, cohort study followed up adults aged 65 years or older in the USA from July 1, 2022, to June 30, 2024, for a first diagnosis of all invasive pneumococcal disease, all pneumococcal pneumonia, all-cause pneumonia, and LRTI identified by ICD-10 Clinical Modification codes. Eligible participants were aged 65 years or older as of Jan 28, 2022 and had at least 1 year of continuous enrolment in Medicare Parts A and B before the index date, which was defined as the first health-care claim for unvaccinated participants and 30 days after PCV20 administration for vaccinated participants. Participants were required to have at least one claim between July 1, 2022, and May 31, 2024, to assign the index date. Individuals who received PCV20 before July 1, 2022 were excluded; corresponding follow-up was excluded if the participant received 23-valent pneumococcal polysaccharide vaccine within 2 years, 13-valent pneumococcal conjugate vaccine within 5 years, or 15-valent pneumococcal conjugate vaccine any time before the index date. Individuals could contribute follow-up as unvaccinated, vaccinated, or both. All data were collected from the Medicare database. Hazard ratios (HRs) were estimated using Cox models with inverse probability of treatment and censoring weights. Vaccine effectiveness was calculated as (1–HR)×100%. Incidence rates (IRs) per 100 000 person-years were estimated using weighted Poisson models and absolute rate reduction during the first year of follow-up was calculated as the difference between unvaccinated and vaccinated IRs. Analyses were stratified by age group and risk group. Findings: Of the 56 888 336 individuals in the Medicare database aged 65 years or older as of Jan 28, 2022, 16 503 552 individuals were included in the study. Of the included individuals, 459 708 (2·8%) contributed PCV20-vaccinated follow-up only, 14 495 239 (87·8%) contributed unvaccinated follow-up only, and 1 548 605 (9·4%) contributed both, which resulted in 2 008 313 individuals in the PCV20-vaccinated group and 16 043 844 individuals in the PCV20-unvaccinated group. In the vaccinated group, 1 149 701 (57·2%) individuals were female and 858 612 (42·8%) were male; in the unvaccinated group, 8 991 239 (56·0%) individuals were female and 7 052 605 (44·0%) were male. 481 212 (24·0%) individuals in the vaccinated group and 3 301 641 (20·6%) individuals in the unvaccinated group were immunocompromised. Adjusted vaccine effectiveness was 25·6% (95% CI 17·4–33·0), 23·3% (16·3–29·8), 15·2% (14·5–15·9), and 7·4% (6·9–7·8) against all invasive pneumococcal disease, all pneumococcal pneumonia, all-cause pneumonia, and LRTI, respectively. During the first year of follow-up, the adjusted absolute rate reduction associated with PCV20 was 12·0 (95% CI 8·0–16·0), 12·8 (8·2–17·4), 758·0 (664·2–851·7), and 636·1 (503·8–768·4) cases per 100 000 person-years for all invasive pneumococcal disease, all pneumococcal pneumonia, all-cause pneumonia, and LRTI, respectively. Interpretation: To our knowledge, our study is the first to generate evidence of PCV20 effectiveness in older adults post-licensure. PCV20 vaccination was associated with a lower risk of all invasive pneumococcal disease, all pneumococcal pneumonia, all-cause pneumonia, and LRTI among adults aged 65 years or older in the USA compared with no PCV20 vaccination. Substantial public health impact was evident within a year of vaccination, driven by reductions in all-cause pneumonia and LRTIs. These real-world results can inform public health decision making for the implementation of national or regional adult pneumococcal vaccination programmes. Funding: Pfizer.