Objective:

To evaluate the relative vaccine effectiveness (rVE) of adjuvanted quadrivalent influenza vaccine (aQIV) versus high-dose quadrivalent influenza vaccine (HD-QIV) for preventing test-confirmed influenza among US adults aged ≥65 years during the 2023–2024 season across any care setting and ED/hospitalization settings, and for preventing test-confirmed influenza hospitalizations in overall and high-risk older adults using pooled 2022–2024 data.

Approach:

• Data Source: Electronic health records supplemented with administrative medical and pharmacy claims from the Optum Market Clarity database were used for the 2023–2024 influenza season, with previously evaluated 2022–2023 data incorporated into the pooled hospitalization analysis.
• Study Design: Retrospective test-negative design including US adults aged ≥65 years who received aQIV or HD-QIV and had an acute respiratory or febrile illness diagnosis with an influenza test occurring within ±7 days. Cases had a positive qualifying influenza test, whereas controls had a negative qualifying test and no positive influenza test during the season.
• Study Objectives: For 2023–2024, rVE was evaluated for prevention of test-confirmed influenza in any setting and in ED/hospitalization settings. Pooled 2022–2024 analyses evaluated test-confirmed influenza hospitalizations overall and among adults with ≥1 CDC-defined high-risk condition.

Key Findings:

• The 2023–2024 analysis included 37,377 vaccinated and tested individuals, comprising 3174 influenza-positive cases and 34,203 test-negative controls.
• In 2023–2024, the rVE of aQIV versus HD-QIV was −0.9% (95% CI, −9.9 to 7.3; P = 0.83) in any setting and 0.5% (95% CI, −12.1 to 11.6; P = 0.94) in ED/hospitalization settings.
• In the pooled 2022–2024 hospitalization analysis, rVE was −0.5% (95% CI, −13.4 to 10.9; P = 0.94) overall and −1.3% (95% CI, −14.4 to 10.4; P = 0.84) among individuals with ≥1 high-risk condition.
• No statistically significant differences in rVE between aQIV and HD-QIV were observed in any analysis, including the pooled high-risk hospitalization subgroup.

Interpretation:

aQIV and HD-QIV showed comparable effectiveness against test-confirmed influenza among adults aged ≥65 years across the evaluated care settings. The findings also support comparable effectiveness for preventing test-confirmed influenza hospitalizations in both the overall and high-risk older adult populations across the pooled 2022–2024 seasons, consistent with previous comparative studies of enhanced influenza vaccines.

Limitations:

• Influenza testing was performed as part of routine care rather than according to predefined screening criteria.
• Detailed information on the specific influenza test used, including RT-PCR versus rapid antigen testing, was not consistently available in the database and could not be evaluated.
• Although a sensitivity analysis suggested that differences between vaccine groups in the likelihood of influenza testing did not meaningfully affect rVE estimates, residual sources of bias cannot be excluded because the study used observational data.

Conclusion:

aQIV and HD-QIV provided comparable protection against test-confirmed influenza in any setting, including ED/hospitalization settings, among adults aged ≥65 years during the 2023–2024 season. Pooled analyses of the 2022–2023 and 2023–2024 seasons likewise showed comparable effectiveness against test-confirmed influenza hospitalizations in the overall population and among older adults with ≥1 high-risk condition.