Absolute and Relative Effectiveness of High-Dose vs Standard-Dose Influenza Vaccines Against Severe Outcomes in Older Adults
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Importance
Several influenza vaccine products are available for older adults, but evidence combining both their absolute effectiveness and head-to-head comparisons within the same large population remains scarce, limiting product-specific vaccination guidance for this high-risk group.
Objective
To estimate the relative and absolute effectiveness of influenza vaccines against influenza- related hospitalization and in-hospital mortality among older adults.
Design, Setting, and Participants
Nationwide cohort study using the French National Health Data System (SNDS), including all adults born in 1958 or earlier, living in metropolitan France, at the start of the 2023-2024 campaign. Relative effectiveness (rVE) was assessed using a landmark design with exposure fixed before epidemic onset. Absolute effectiveness (VE) was assessed using a sequential trial emulation with weekly matching of newly vaccinated individuals to yet unvaccinated controls. Follow-up ran from December 5, 2023 to April 19, 2024.
Exposures
Vaccination with a high-dose (Efluelda) or one of three standard-dose quadrivalent vaccines (Influvac, Fluarix, Vaxigrip), compared individually or by dosage category, and against no vaccination.
Main Outcomes and Measures
Hospitalization with a diagnosis of influenza and death during such hospitalization. Effectiveness was estimated as 1 minus the hazard ratio from weighted Cox models, with corresponding numbers needed to vaccinate to prevent one case.
Results
Among 13.8 million eligible individuals, 5.7 million (41%) were vaccinated at the beginning of follow-up. The high-dose vaccine showed greater rVE than standard-dose vaccines against hospitalization (27% [95%CI, 23 to 31%]) and in-hospital death (27% [95%CI,14 to 38%]). Absolute VE was 39% (95%CI, 38 to 41%) against hospitalization and 45% (95%CI, 40 to 49%) against in-hospital death, and was higher for the high-dose vaccine (50%) than standard-dose vaccines (36%) against hospitalization. This difference was most evident among adults 70 years and older, while overall effectiveness declined with age.
Conclusions and Relevance
In this study, influenza vaccination conferred moderate protection against severe outcomes in older adults, and high-dose vaccination was associated with significantly greater effectiveness than standard-dose vaccines, particularly among adults 70 years and older. These findings support product-level differentiation in vaccination strategy for this population.
Key points
Question
What is the absolute effectiveness of influenza vaccination and the relative effectiveness of high-dose versus standard-dose vaccines against severe influenza outcomes in older adults?
Findings
In this nationwide cohort study of 13.8 million older adults in France, vaccination was associated with 39% lower risk of influenza-related hospitalization and 45% lower risk of death during those hospitalizations compared with no vaccination. The high-dose vaccine was associated with greater absolute effectiveness than standard-dose vaccines against hospitalization (50% vs 36%), a difference most evident among adults 70 years and older, and with significantly greater relative effectiveness against hospitalization (27%) as well.
Meaning
These findings suggest that high-dose influenza vaccination provides added protection over standard-dose formulations in older adults, particularly from age 70 onward, and may support product-specific vaccination recommendations for this population.
