Relative Vaccine Efficacy of High-Dose Versus Standard-Dose Influenza Vaccines in Preventing Probable Influenza in a Medicare Fee-for-Service Population

Abstract

Background: High-dose (HD) influenza vaccine, currently the most commonly used vaccine among US seniors (aged ≥ 65 years), has been shown to be more efficacious than standard-dose (SD) vaccine in multiple randomized trials. This study evaluated the real-world relative vaccine effectiveness (rVE) of HD vs SD over four influenza seasons. Methods: This study included Medicare Fee-for-Service enrollees who received HD or SD at an outpatient clinic or pharmacy during influenza seasons 2011-12 through 2014-15. Probable influenza (an inpatient stay with an influenza diagnosis on the claim, or an outpatient visit with a rapid influenza test/culture followed by an antiviral prescription) was assessed among HD recipients matched 1:1 with SD recipients by location, vaccination date, age, and sex. Fine-Gray subdistribution hazard models with competing risk of death were used to adjust for residual confounding. Analyses were stratified by outpatient vs pharmacy vaccination. Findings: Across the four influenza seasons, there were 535,598, 1,017,552, 1,548,164, and 2,420,450 in the pharmacy cohort; and 821,662, 1,151,080, 1,559,488, and 2,421,758 in the outpatient cohort. During peak influenza season, rVEs for 2011-12 through 2014-15 were 21·8% (95% CI: -5·9%, 42·3%), 14·8% (9·3%, 19·9%), 16·9% (9·2%, 23·9%), and 17·2% (14·5%, 19·9%), respectively, in the pharmacy cohort; and 16·5% (-5·9%, 34·2%), 15·1% (10·9%, 19·1%), 10·0% (2·9%, 16·6%), and -0·2% (-3·0%, 2·5%), respectively, in the outpatient cohort. Interpretation: HD was consistently associated with better protection against probable influenza. The lower treatment effect observed in the outpatient cohort could reflect provider bias due to physicians triaging HD to frailer patients. Funding Statement: This study was supported by Sanofi Pasteur (Swiftwater, PA). Declaration of Interests: A.C. is an employee of Sanofi Pasteur (Swiftwater, PA, USA), the funder of this study. M.P., A.B., S.K., D.V., and L.B. are employees of Optum (Eden Prairie, MN, USA), which was contracted by Sanofi Pasteur to conduct this study and provide medical writing support. SMM has received unrestricted research grants from Merck, GlaxoSmithKline, Sanofi Pasteur, Pfizer and Roche-Assurex for unrelated studies. SMM has received fees as an advisory board member for Sanofi Pasteur. Ethics Approval Statement: This study was approved by the New England Institutional Review Board (approval #120160896), with waived consent for analyses of deidentified administrative claims.