Comparative effectiveness of high-dose versus standard-dose influenza vaccines in US residents aged 65 years and older from 2012 to 2013 using Medicare data: a retrospective cohort analysis

Abstract

Background: A high-dose trivalent inactivated influenza vaccine was licensed in 2009 by the US Food and Drug Administration (FDA) on the basis of serological criteria. We sought to establish whether high-dose inactivated influenza vaccine was more effective for prevention of influenza-related visits and hospital admissions in US Medicare beneficiaries than was standard-dose inactivated influenza vaccine.

Methods: In this retrospective cohort study, we identified Medicare beneficiaries aged 65 years and older who received high-dose or standard-dose inactivated influenza vaccines from community pharmacies that offered both vaccines during the 2012-13 influenza season. Outcomes were defined with billing codes on Medicare claims. The primary outcome was probable influenza infection, defined by receipt of a rapid influenza test followed by dispensing of the neuraminidase inhibitor oseltamivir. The secondary outcome was a hospital or emergency department visit, listing a Medicare billing code for influenza. We estimated relative vaccine effectiveness by comparing outcome rates in Medicare beneficiaries during periods of high influenza circulation. Univariate and multivariate Poisson regression models were used for analyses.

Findings: Between Aug 1, 2012 and Jan 31, 2013, we studied 929,730 recipients of high-dose vaccine and 1,615,545 recipients of standard-dose vaccine. Participants enrolled in each cohort were well balanced with respect to age and presence of underlying medical disorders. The high-dose vaccine (1·30 outcomes per 10,000 person-weeks) was 22% (95% CI 15-29) more effective than the standard-dose vaccine (1·01 outcomes per 10,000 person-weeks) for prevention of probable influenza infections (rapid influenza test followed by oseltamivir treatment) and 22% (95% CI 16-27%) more effective for prevention of influenza hospital admissions (0·86 outcomes per 10,000 person-weeks in the high-dose cohort vs 1·10 outcomes per 10,000 person-weeks in the standard-dose cohort).

Interpretation: Our retrospective cohort study in US Medicare beneficiaries shows that, in people 65 years of age and older, high-dose inactivated influenza vaccine was significantly more effective than standard-dose vaccine in prevention of influenza-related medical encounters. Additionally, the large population in our study enabled us to show, for the first time, a significant reduction in influenza-related hospital admissions in high-dose compared to standard-dose vaccine recipients, an outcome not shown in randomised studies. These results provide important new information to be considered by policy makers recommending influenza vaccinations for elderly people.

Funding: FDA and the office of the Assistant Secretary of Planning and Evaluation.

Conflict of interest statement

Declaration of interests

We declare no competing interests.

Copyright © 2015 Elsevier Ltd. All rights reserved.

Figures

Figure 1. Influenza outcome rates by vaccine type during the 2012–13 influenza season

Each plot displays the rate of influenza per 10 000 person-weeks. Data was smoothed using a weighted average, placing a weight of 0·5 on the current week and a weight of 0·25 on the previous and following weeks. (A) Rapid influenza test followed by treatment with oseltamivir. (B) Inpatient hospital admissions or emergency department visits with an influenza International Classification of Diseases, ninth revision, Clinical Modification code. RIT=rapid influenza diagnostic test.

Figure 2. Influenza outcome rates in the 2012–13 influenza season

Each plot displays the rate of influenza per 10 000 person-weeks. (A) Community setting medical encounters including a rapid influenza test followed by treatment with oseltamivir. (B) Inpatient hospital admissions or emergency department visits with an influenza International Classification of Diseases, ninth revision, Clinical Modification code. Both graphs show the rates for the entire cohort (=65 years) and for the cohort stratified into three age groups (65–74 years, 75–84 years, and =85 years). The rates are shown for three periods during the season—high, medium, and low circulation. RIT=rapid influenza diagnostic test.

Figure 3. Relative vaccine effectiveness for different outcomes during the 2012–13 high influenza season

Shown are relative effectiveness and 95% CIs for two influenza outcomes. The top outcome is the measure of community medical encounters including a rapid influenza test followed by treatment with oseltamivir, and the bottom outcome is the measure of inpatient hospital admissions or emergency department visits with an International Classification of Diseases, ninth revision, Clinical Modification influenza code. For each outcome, we reported relative effectiveness for the entire cohort and for the cohort stratified into three age groups (65–74 years, 75–84 years, and =85 years). RIT=rapid influenza diagnostic test.