Effectiveness of high-dose influenza vaccine against hospitalisations in older adults (FLUNITY-HD): an individual-level pooled analysis.

Summary

Across 466,320 randomized participants, high-dose influenza vaccine reduced hospitalisation for influenza or pneumonia versus standard dose (relative vaccine effectiveness 8.8%). It also reduced cardiorespiratory, laboratory-confirmed influenza, and all-cause hospitalisations, with similar all-cause mortality and serious adverse events.

Key Findings

• Primary endpoint: hospitalisation for influenza or pneumonia was lower with HD-IIV vs SD-IIV (rVE 8.8%, 95% CI 1.7–15.5; one-sided p=0.0082).
• Secondary endpoints: reductions with HD-IIV in cardiorespiratory hospitalisation (rVE 6.3%), laboratory-confirmed influenza hospitalisation (rVE 31.9%), and all-cause hospitalisation (rVE 2.2%).
• All-cause mortality and serious adverse events were similar between groups.

Clinical Implications

Preferential use of high-dose inactivated influenza vaccine in older adults may reduce influenza/pneumonia and cardiorespiratory hospitalizations without increasing serious adverse events, and should be considered in immunization programs.

Limitations

• Geographic scope limited to Denmark and Galicia (Spain), potentially affecting generalizability.
• No mortality benefit demonstrated; potential confounding by circulating strains across seasons.

Future Directions

Head-to-head cost-effectiveness analyses and implementation studies across diverse health systems; evaluation in very old, frail, or multimorbid populations and in coadministration settings.