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Comparative Study
. 2024 Nov 22;79(5):1283-1292.
doi: 10.1093/cid/ciae375.

Comparative Effectiveness of Licensed Influenza Vaccines in Preventing Influenza-related Medical Encounters and Hospitalizations in the 2022-2023 Influenza Season Among Adults ≥65 Years of Age

Jennifer H Ku  1 , Emily Rayens  1 , Lina S Sy  1 , Lei Qian  1 , Bradley K Ackerson  1 , Yi Luo  1 , Julia E Tubert  1 , Gina S Lee  1 , Punam P Modha  1 , Yoonyoung Park  2 , Tianyu Sun  2 , Evan J Anderson  2 , Hung Fu Tseng  1   3
Affiliations
Comparative Study

Comparative Effectiveness of Licensed Influenza Vaccines in Preventing Influenza-related Medical Encounters and Hospitalizations in the 2022-2023 Influenza Season Among Adults ≥65 Years of Age

Jennifer H Ku et al. Clin Infect Dis. .

Abstract

Background: Influenza causes substantial morbidity, particularly among older individuals. Updated data on the effectiveness of currently licensed vaccines in this population are needed.

Methods: At Kaiser Permanente Southern California, we conducted a retrospective cohort study to evaluate comparative vaccine effectiveness (cVE) of high-dose (HD), adjuvanted, and standard-dose (SD) cell-based influenza vaccines, relative to the SD egg-based vaccine. We included adults aged ≥65 years who received an influenza vaccine between 1 August 2022 and 31 December 2022, with follow-up up to 20 May 2023. Primary outcomes were: (1) influenza-related medical encounters and (2) polymerase chain reaction (PCR)-confirmed influenza-related hospitalization. Adjusted hazard ratios (aHR) were estimated by Cox proportional hazards regression, adjusting for confounders using inverse probability of treatment weighting (IPTW). cVE (%) was calculated as (1-aHR) × 100 when aHR ≤1, and ([1/aHR]-1) × 100 when aHR >1.

Results: Our study population (n = 495 119) was 54.9% female, 46.3% non-Hispanic White, with a median age of 73 years (interquartile range [IQR] 69-79). Characteristics of all groups were well balanced after IPTW. Adjusted cVEs against influenza-related medical encounters in the HD, adjuvanted, and SD cell-based vaccine groups were 9.1% (95% confidence interval [CI]: .9, 16.7), 16.9% (95% CI: 1.7, 29.8), and -6.3 (95% CI: -18.3, 6.9), respectively. Adjusted cVEs against PCR-confirmed hospitalization in the HD, adjuvanted, and SD cell-based groups were 25.1% (95% CI: .2, 43.8), 61.6% (95% CI: 18.1, 82.0), and 26.4% (95% CI: -18.3, 55.7), respectively.

Conclusions: Compared to the SD egg-based vaccine, HD and adjuvanted vaccines conferred additional protection against influenza-related outcomes in the 2022-2023 season in adults ≥65 years. Our results provide real-world evidence of the comparative effectiveness of currently licensed vaccines.

Keywords: epidemiology; influenza; influenza vaccine; influenza-related medical encounters; vaccine effectiveness.

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Conflict of interest statement

Potential conflicts of interests. J. H. K., E. R., L. S. S., L. Q., B. K. A., Y. L., J. E. T., G. S. L., P. P. M., and H. F. T. are employees of Kaiser Permanente Southern California, which has been contracted by Moderna, Inc. to conduct this study. Y. P., T. S., and E. J. A., are employees of and shareholders in Moderna, Inc. J. H. K. received funding from GlaxoSmithKline and Moderna unrelated to this manuscript. E. R. received funding from GlaxoSmithKline unrelated to this manuscript. L. S. S. received funding from GlaxoSmithKline, Dynavax, and Moderna unrelated to this manuscript. L. Q. received funding from GlaxoSmithKline, Dynavax, and Moderna unrelated to this manuscript. B. K. A. received funding from GlaxoSmithKline, Dynavax, Genentech, and Moderna unrelated to this manuscript. Y. L. received funding from GlaxoSmithKline, Pfizer, and Moderna unrelated to this manuscript. J. E. T. received funding from GlaxoSmithKline and Moderna unrelated to this manuscript. G. S. L. received funding from GlaxoSmithKline and Moderna unrelated to this manuscript. P. P. M. received funding from GlaxoSmithKline unrelated to this manuscript. H. F. T. received funding from GlaxoSmithKline and Moderna unrelated to this manuscript; H. F. T. also served on advisory boards for Janssen and Pfizer. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Flow diagram for the analytic cohort. Abbreviations: KPSC, Kaiser Permanente Southern California; PCR, polymerase chain reaction; SD, standard dose. aInfluenza vaccines of interest for the exposure included SD egg-based (CVX 150 and 158), high dose (CVX 197), SD cell-based (CVX 171 and 186), and adjuvanted (CVX 205). bIndex date was defined as the date of the first dose of influenza vaccine received during the accrual period, based on the CVX codes above. Non-index influenza vaccinations were not limited to the CVX codes above for identifying influenza vaccinations prior to index date (for exclusion criteria and covariates) and after index date (for censoring).
Figure 2.
Figure 2.
Comparison of absolute standardized difference among influenza vaccine recipients ≥65 y of age, before and after inverse probability of treatment weighting. Abbreviations: COVID-19, coronavirus disease 2019; IPTW, inverse probability of treatment weighting. Chronic respiratory disease includes chronic obstructive pulmonary disease, chronic bronchitis, or emphysema.
Figure 3.
Figure 3.
Forest plot: adjusted cVE for high-dose, adjuvanted, and SD cell-based influenza vaccines, compared to SD egg-based vaccine. Abbreviations: CI, confidence interval; cVE, comparative vaccine effectiveness (vs SD egg-based); PCR, polymerase chain reaction; SD, standard dose. When the hazard ratio or its 95% CI was >1, the cVE (%) or its 95% CI was transformed as ([1/hazard ratio]—1) × 100. aWeighted using stabilized inverse probability of treatment weights. bA positive influenza PCR test; or influenza-related medical encounter in the outpatient, inpatient, emergency, or virtual visit setting identified based on the US Armed Forces Health Surveillance Center Code Set B [22] for influenza without an influenza PCR-negative test ±3 d of the code date. cPCR-confirmed influenza-related hospitalization (a positive PCR test collected between −14 and +3 d from the inpatient admission date) with an acute respiratory infection code [23].
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