Relative Effectiveness of MF59 Adjuvanted Trivalent Influenza Vaccine vs Nonadjuvanted Vaccines During the 2019–2020 Influenza Season

Abstract

Background Age-related immunosenescence may impair the immune response to vaccination in older adults. Adjuvanted influenza vaccines are designed to overcome immune senescence in older adults. This study estimated the relative vaccine effectiveness (rVE) of MF59®-adjuvanted trivalent inactivated influenza vaccine (aIIV3) versus egg-derived quadrivalent inactivated influenza vaccine (IIV4e) and high-dose trivalent inactivated influenza vaccine (HD-IIV3) in preventing influenza-related medical encounters in the 2019-2020 US season. Methods This retrospective cohort study used electronic medical records linked to pharmacy and medical claims data. The study population included adults age ≥65 years with a record of aIIV3, IIV4e, or HD-IIV3 vaccination. A doubly robust inverse probability of treatment weighting model was used to derive adjusted odds ratios (OR). rVE was calculated by (1–ORadjusted)*100 and was determined overall and separately for age subgroups. An exploratory analysis evaluated the outcome separately in inpatient and outpatient settings. Results Subjects received aIIV3 (n=936,508), IIV3e (n=651,034), and HD-IIV3 (n=1,813,819) and influenza-related medical encounters were recorded in 0.5%, 0.9%, 0.7% of each cohort, respectively. Overall, rVE of aIIV3 was 27.5% (95% CI, 24.4 to 30.5) versus IIV4e and 13.9% (95% CI 10.7 to 17.0) vs versus HD-IIV3. aIIV3 had a more favorable rVE in inpatient and outpatient settings. Findings remained consistent across age subgroups and during alternative seasonal dates. Conclusions Adults ≥65 years vaccinated with aIIV3 had fewer influenza-related medical encounters compared with IIV4e or HD-IIV3 during the 2019-2020 US influenza season.

Review of Analyses Estimating Relative Vaccine Effectiveness of Cell-Based Quadrivalent Influenza Vaccine in Three Consecutive US Influenza Seasons

“…The dataset for each retrospective cohort study included only de-identified clinical data that met Protected Health Information (PHI) data requirements and were certified for Health Insurance Portability and Accountability Act (HIPAA) compliance. The studies were conducted and reported in accordance with Good Pharmacoepidemiological Practice from the Declaration of Helsinki, which is applicable to local regulations, and the Reporting of Studies Conducted using Observational Routinely Collected Health Data (RECORD) [22][23][24][25][26]28].…”

“…During the next season, subjects were vaccinated from 1 August 2018 through 28 February 2019 and the observation period was 1 August 2018 through 18 May 2019 [23]. In the 2019-2020 season, subjects were vaccinated from 1 August 2019 through 31 January 2020 and the observation period was 29 September 2019 through 7 March 2020-an early cut-off to avoid potential bias arising from the coronavirus disease 2019 (COVID-19) pandemic [25,26]. Overall inpatient or outpatient influenza-related medical encounters (IRMEs)-the primary outcome in all studies-were defined using the International Classification of Diseases (ICD)-9-CM and ICD-10-CM codes that correspond to the US Armed Forces Health Surveillance Center (AFHSC) Code Set B (Table S2) [29].…”

“…For all seasons, rVE was determined using the formula (% VE = 1 − OR adjusted ) × 100. Additional details on the statistical methods can be found in the original publications [22][23][24][25][26].…”

“…In this review, we discuss the relative vaccine effectiveness (rVE) of IIV4c versus IIV4e in children and adults over three consecutive influenza seasons from 2017 to 2020, as well as the epidemiological characteristics of each season. The rVE for each season was estimated based on the same underlying EMR dataset for all three seasons, with the addition of linked claims for the latter two seasons [22][23][24][25][26]. While the RWE evaluations of the rVE of IIV4c versus IIV4e may be best done in the context of the entire available body of evidence, disentangling the relative contributions of study design and season-specific effects on variations in the observed rVE presents a complex challenge.…”

“…study populations (individual characteristics had frequency of >50%) included female sex, ethnicity/race of non-Hispanic/white, and residence in the southern US. Additional demographic details can be found in the original publications [22,23,25,26]. IIV4c performed better than IIV4e in the prevention of IRMEs in the overall population and in the pediatric and adult subgroups over the three consecutive US influenza seasons, except for the 4-17-year age group in 2017-2018 and adults ≥65 years old in all seasons.…”