@article{3003164, title = "Systematic review of the efficacy, effectiveness and safety of high-dose seasonal influenza vaccines for the prevention of laboratory-confirmed influenza in individuals ≥18 years of age", author = "Comber, L. and O Murchu, E. and Jordan, K. and Hawkshaw, S. and Marshall, L. and O'Neill, M. and Teljeur, C. and Ryan, M. and Carnahan, A. and Pérez Martín, J.J. and Robertson, A.H. and Johansen, K. and de Jonge, J. and Krause, T. and Nicolay, N. and Nohynek, H. and Pavlopoulou, I. and Pebody, R. and Penttinen, P. and Soler-Soneira, M. and Wichmann, O. and Harrington, P.", journal = "Reviews in Medical Virology", year = "2022", publisher = "John Wiley and Sons Ltd", issn = "1052-9276, 1099-1654", doi = "10.1002/rmv.2330", abstract = "This review sought to assess the efficacy, effectiveness and safety of high-dose inactivated influenza vaccines (HD-IIV) for the prevention of laboratory-confirmed influenza in individuals aged 18 years or older. A systematic literature search was conducted in electronic databases and grey literature sources up to 7 February 2020. Randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) were included. The search returned 28,846 records, of which 36 studies were included. HD-IIV was shown to have higher relative vaccine efficacy in preventing influenza compared with standard-dose influenza vaccines (SD-IIV3) in older adults (Vaccine effectiveness (VE) = 24%, 95% CI 10–37, one RCT). One NRSI demonstrated significant effect for HD-IIV3 against influenza B (VE = 89%, 95% CI 47–100), but not for influenza A(H3N2) (VE = 22%, 95% CI −82 to 66) when compared with no vaccination in older adults. HD-IIV3 showed significant relative effect compared with SD-IIV3 for influenza-related hospitalisation (VE = 11.8%, 95% CI 6.4–17.0, two NRSIs), influenza- or pneumonia-related hospitalisation (VE = 13.7%, 95% CI 9.5–17.7, three NRSIs), influenza-related hospital encounters (VE = 13.1%, 95% CI 8.4–17.7, five NRSIs), and influenza-related office visits (VE = 3.5%, 95% CI 1.5–5.5, two NRSIs). For safety, HD-IIV were associated with significantly higher rates of local and systemic adverse events compared with SD-IIV (combined local reactions, pain at injection site, swelling, induration, headache, chills and malaise). From limited data, compared with SD-IIV, HD-IIV were found to be more effective in the prevention of laboratory-confirmed influenza, for a range of proxy outcome measures, and associated with more adverse events. © 2022 John Wiley & Sons Ltd." }