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

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.