Efficacy and Effectiveness of High-Dose Influenza Vaccine for Older Adults: A Systematic Review and Meta-Analysis

BACKGROUND: Seasonal influenza epidemics are responsible for significant disease burden each year, especially in adults over the age of 65. Only recently have there been vaccines that are formulated specifically for individuals 65 years of age or older, one of which, Fluzone(®)High-Dose (IIV3-HD), has received widespread use in the US. This study aims to review the evidence of efficacy and effectiveness of IIV3-HD compared with standard dose influenza vaccine (IIV3) in individuals aged 65 years or older against clinical outcomes plausibly related to influenza. METHODS: A systematic review of four electronic databases and other sources was conducted for randomized and observational studies assessing vaccine efficacy or effectiveness (VE) of IIV3-HD against clinical outcomes such as influenza-like illness, hospital admissions and death in adults 65 years of age or older. A meta-analysis was conducted by separately extracting individual VEs reported in the studies and estimating random-effects pooled efficacy against each of the clinical outcomes. RESULTS: 7 eligible studies (4 randomized trials and 3 observational studies) were identified following the screening of 1,816 studies. All of these studies reported relative VE (rVE) of IIV3-HD vs. IIV3, and not absolute efficacy/effectiveness of IIV3-HD. Of those, 5 studies reported rVE for IIV3-HD vs. IIV3 against influenza-like illness, 6 studies reported rVE against hospital admissions, and 3 studies reported rVE against death. IIV3-HD demonstrated improved protection against influenza-like illness (rVE=18.3%, 95% CI: 7.0 to 28.3%), and was also more effective at preventing hospital admissions due to influenza illness (rVE=19.4%, 95% CI: 6.7 to 30.4%), pneumonia (rVE=22.4%, 95% CI: 5.0 to 36.5%), cardiorespiratory events (rVE=12.0%, 95% CI: 4.9 to 18.6%), and death following a hospital admission for influenza (rVE=22.2%, 95% CI: -18.2 to 48.8%). IIV3 also had a modest but not statistically significant impact on all-cause hospital admissions (rVE= 7.3%, 95% CI: -1.5 to 15.4%) and all-cause death (rVE=0.8%, 95% CI: -4.2 to 5.5%). CONCLUSION: There is significant evidence demonstrating IIV3-HD is more effective than standard dose influenza vaccine at reducing the clinical outcomes typically associated with influenza infection in older adults. This study was funded by sanofi pasteur. DISCLOSURES: J. Lee, sanofi pasteur: Employee, Salary; G. Lam, sanofi pasteur: Employee, Salary; T. Shin, sanofi pasteur: Employee, Salary; J. Kim, sanofi pasteur: Co-op Student, Educational support; A. Krishnan, sanofi pasteur: Co-op Student, Educational support; B. Seet, sanofi pasteur: Employee and Shareholder, Salary; D. Neame, sanofi pasteur: Employee and Shareholder, Salary; D. P. Greenberg, sanofi pasteur: Employee and Shareholder, Salary; A. Chit, sanofi pasteur: Employee, Salary