This study estimated the relative vaccine effectiveness (rVE) of the MF59®-adjuvanted trivalent influenza vaccine (aTIV) versus standard-dose nonadjuvanted egg-based quadrivalent influenza vaccines (QIVe) for the prevention of influenza-related medical encounters (IRMEs), outpatient IRMEs, and influenza- and pneumonia-related hospitalizations during the 2019-2020 US influenza season among adults ≥65 years of age who had ≥1 high-risk condition. A secondary objective evaluated the rVE of aTIV versus QIVe in preventing these outcomes among older adults with specific high-risk conditions. This retrospective cohort study included US adults ≥65 years of age vaccinated with aTIV or QIVe between August 1, 2019, and January 31, 2020. Exposures, covariates, risk factors, and outcomes were captured from a linked dataset comprised of electronic health records (EHR) (Veradigm Network EHR) linked to insurance claims (Komodo Healthcare Map). A doubly robust approach was applied wherein multivariable-adjusted odds ratios were derived using inverse probability of treatment-weighted samples to calculate rVEs and 95 % confidence interval independently for individuals ≥1 high-risk condition and those with specific high-risk conditions. The study included 954,707 aTIV and 719,125 QIVe recipients. For all outcomes, aTIV was more effective than QIVe among adults ≥65 years of age who had ≥1 high-risk condition (any IMRE: 23.6 % [20.9 %-26.1 %]), outpatient IRME: 23.3 % [20.4 %-26.1 %], and influenza- or pneumonia-related hospitalizations: 19.0 % [16.3 %-21.6 %]), during the 2019-2020 influenza season. Similarly, aTIV was more effective than QIVe at preventing outcomes among individuals with specific high-risk conditions except for body mass index ≥40. This study demonstrated higher effectiveness of aTIV versus QIVe in preventing any IRMEs, outpatient IRMEs, and influenza- or pneumonia-related hospitalizations among adults ≥65 years of age who had ≥1 high-risk condition.
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