The relative effectiveness of a high-dose quadrivalent influenza vaccine versus standard-dose quadrivalent influenza vaccines in older adults in France: a retrospective cohort study during the 2021-2022 influenza season

Objectives: High-dose quadrivalent influenza vaccine (HD-QIV) was introduced during the 2021/2022 influenza season in France for adults aged ≥65 years as an alternative to standard-dose quadrivalent influenza vaccine (SD-QIV). The aim of this study is to estimate the relative vaccine effectiveness of HD-QIV vs. SD-QIV against influenza-related hospitalizations in France.

Methods: Community-dwelling individuals aged ≥65 years with reimbursed influenza vaccine claims during the 2021/2022 influenza season were included in the French national health insurance database. Individuals were followed up from vaccination day to 30 June 2022, nursing home admission or death date. Baseline socio-demographic and health characteristics were identified from medical records over the five previous years. Hospitalizations for influenza and other causes were recorded from 14 days after vaccination until the end of follow-up. HD-QIV and SD-QIV vaccinees were matched using 1:4 propensity score matching with an exact constraint on age group, sex, week of vaccination, and region. Incidence rate ratios were estimated using zero-inflated Poisson or zero-inflated negative binomial regression models.

Results: We matched 405 385 HD-QIV to 1 621 540 SD-QIV vaccinees. HD-QIV was associated with a 23.3% (95% CI, 8.4-35.8) lower rate of influenza hospitalizations compared with SD-QIV (69.5/100 000 person years vs. 90.5/100 000 person years). Post-matching, we observed higher rates in the HD-QIV group for hospitalizations non-specific to influenza and negative control outcomes, suggesting residual confounding by indication.

Discussion: HD-QIV was associated with lower influenza-related hospitalization rates vs. SD-QIV, consistent with existing evidence, in the context of high SARS-CoV-2 circulation in France and likely prioritization of HD-QIV for older/more comorbid individuals.