Efficacy and effectiveness of high-dose versus standard-dose influenza vaccination for older adults: a systematic review and meta-analysis

Background: Influenza is responsible for a significant disease burden annually, especially in older adults. This study reviews the relative vaccine efficacy or effectiveness (rVE) of high-dose inactivated trivalent influenza vaccine (HD-IIV3) compared to standard-dose influenza vaccines (SD-IIV3) in adults ≥65 against influenza-associated outcomes to inform evidence-based decision-making to shift clinical practice and standard of care in this population. Methods: A systematic review was conducted for studies assessing the rVE of HD-IIV3 against probable/laboratory-confirmed influenza-like illness (ILI), hospital admissions, and death in adults ≥65. Results from individual seasons were meta-analyzed and a random-effects model was used to estimate pooled rVEs. Results: After screening 992 studies, seven studies were meta-analyzed. HD-IIV3 demonstrated better protection against ILI compared to SD-IIV3 (rVE = 19.5%; 95% CI: 8.6–29.0%). HD-IIV3 was also more effective at preventing hospital admissions from all-causes (rVE = 9.1%; 95% CI: 2.4–15.3%), as well as from influenza (rVE = 17.8%; 95% CI: 8.1–26.5%), pneumonia (rVE = 24.3%, 95% CI: 13.9–33.4%), and cardiorespiratory events (rVE = 18.2%; 95% CI: 6.8–28.1%). rVE against post-influenza mortality was 22.2% (95% CI: -18.2–48.8%) and 2.5% (95% CI: -5.2–9.5%) against all-cause mortality. Conclusions: Available evidence suggests HD-IIV3 is more effective than SD-IIV3 at reducing the clinical outcomes associated with influenza infection in older adults and should be considered for routine use in the 65+ population.