Adjuvanted and high-dose influenza vaccine showed similar effectiveness against laboratory-confirmed influenza among adults aged 65 years or older during the 2023-2024 influenza season, according to a large pragmatic study. The findings support current Advisory Committee on Immunization Practices recommendations supporting either vaccine formulation for older adults.

The study represents the first season of an ongoing 2-season comparative effectiveness analysis of adjuvanted vs high-dose influenza vaccines in routine clinical care. Researchers said the findings support continued use of either formulation in adults aged 65 years or older, although pooled analyses across both seasons are still pending.

Researchers evaluated 429,595 Kaiser Permanente Northern California patients aged 65 years or older who received either adjuvanted or high-dose inactivated influenza vaccine between August 17, 2023, and April 16, 2024. The study used a pragmatic cluster randomized crossover design in which 65 Kaiser Permanente Northern California facilities alternated weekly between administering adjuvanted and high-dose vaccine formulations after an initial randomized assignment at the beginning of the vaccination season.

Unlike a traditional individually randomized clinical trial, patients were not prospectively enrolled or individually assigned to a vaccine type. Instead, vaccine receipt depended on the facility and week in which patients sought vaccination, and researchers retrospectively identified eligible vaccinated patients from routine care data.

The primary outcome was polymerase chain reaction-confirmed influenza occurring at least 14 days after vaccination in any clinical setting. Secondary outcomes included polymerase chain reaction-confirmed influenza associated with hospitalization or emergency department visits and hospitalization for all-cause community-acquired pneumonia. Outcomes were assessed beginning October 1, 2023, or 14 days after vaccination, whichever occurred later.

Among the study population, 212,875 patients received adjuvanted vaccine and 216,720 received high-dose vaccine. The mean age was 75 years, and 55% were women. Baseline demographic and clinical characteristics were well-balanced between groups.

During follow-up, 836 patients who received adjuvanted vaccine and 867 patients who received high-dose vaccine developed polymerase chain reaction-confirmed influenza, corresponding to approximately 4 cases per 1,000 patients in each group. Influenza A accounted for 98% of cases in the adjuvanted group and about 99% in the high-dose group.

Adjusted relative vaccine effectiveness for adjuvanted vs high-dose vaccine was 1.5% against polymerase chain reaction-confirmed influenza, with no statistically significant difference between formulations. The prespecified noninferiority margin required the lower bound of the 95% confidence interval for relative vaccine effectiveness to remain above −20%.

For secondary outcomes, relative vaccine effectiveness for adjuvanted vs high-dose vaccine was 9% against polymerase chain reaction-confirmed influenza associated with hospitalization or emergency department visits and 1% against hospitalization for all-cause community-acquired pneumonia. Confidence intervals for both secondary outcomes crossed zero, indicating no statistically significant difference between formulations, although all analyses met prespecified noninferiority criteria.

Researchers noted that the numerically favorable 9% estimate for influenza-associated hospitalization or emergency department visits may warrant further evaluation when pooled 2-season analyses become available, although the current study was not powered to demonstrate superiority for that endpoint.

Analyses were adjusted for age, sex, race and ethnicity, comorbidities, prior health care utilization, and prior influenza vaccination. Analyses also conditioned risk sets on calendar date and stratified by facility to account for local influenza circulation and geographic variation.

Sensitivity analyses accounting for clustering by facility and vaccination week produced results consistent with the primary analysis.

The researchers noted several limitations. Facilities were not required to switch vaccine stock precisely at the beginning of each week, and some patients may have requested a specific vaccine formulation, introducing the possibility of imperfect adherence to the randomized crossover schedule. In addition, although polymerase chain reaction testing rates were similar between groups, the study could not assess testing propensity according to symptom severity, potentially underrepresenting milder influenza cases.

The findings also may not generalize to uninsured populations or regions outside Northern California, and results could differ in influenza seasons with poorer vaccine-strain matching or different circulating strains. The 2023-2024 season was predominantly driven by influenza A.

The study was funded by CSL Seqirus, manufacturer of the adjuvanted influenza vaccine Fluad, which also donated vaccine doses used in routine clinical care. Several authors reported employment or stock ownership with CSL Seqirus.The company had no role in data collection, analysis, interpretation, or publication decisions.

The researchers concluded that adjuvanted and high-dose influenza vaccines showed similar effectiveness during the first season of the ongoing study, supporting continued inclusion of both formulations in preferential influenza vaccine recommendations for adults aged 65 years or older.

Disclosures can be found in the study.

Source: JAMA Network Open