Is There a Place for First-Generation mRNA Seasonal Influenza Vaccines? Unraveling the Clinical and Economic Consequences of Increased Reactogenicity in U.S. Older Adults

OBJECTIVES: Clinical trials (CT) of first-generation influenza messenger ribonucleic acid (mRNA) vaccines have demonstrated comparable immune response to standard inactivated (egg-based or recombinant) influenza vaccines, accompanied by substantially higher rates of post-vaccination reactions. We modeled the potential clinical and economic consequences of reactogenicity and vaccination hesitancy among older adults aged 65+ years in the United States (US).

METHODS: One-year disease-transition model mirroring the course of immunized individuals, considering reactogenicity and the consequences of influenza in those infected, from a payor perspective. Model inputs were informed by US-specific demographics, epidemiology, and direct costs expressed in constant 2023 US$. Equal vaccine acquisition cost and efficacy across technologies was assumed. Healthcare-seeking behavior was classified as non-medically or outpatient attended, for grades 1-2 and 3 reactions, respectively. Model outputs present deterministic scenarios of post-vaccination reactions based on a range of early phase mRNA CT results (+/-10%), market penetration (10%-30%), and vaccination hesitancy (10- 30%) affecting vaccination coverage rates (VCR).

RESULTS: The introduction of mRNA vaccines up to 30% market share would increase, on average, 164% (range 145-184) the number of post-vaccination Grade 3 reactions, leading to additional 0.6million (m, 0.5-0.7) medical events. This scenario equates to $13.5m (10.8-16.4) in added outpatient costs. The supplementary number of patients experiencing Grade 1-2 reactions would range from 3.0m (2.5-3.6m [+12%]) to 9.0m (7.4-10.7m [+37%]) for market share scenarios of 10% and 30%, respectively. When simultaneously varying mRNA market shares and vaccination hesitancy, an increased frequency in inpatient and outpatient visits, and deaths could be expected, varying from 0.8% to 6.8% for the scenarios raising 10% and 30%, respectively.

CONCLUSIONS: Modeling early mRNA influenza vaccination CT into cases and costs scaled at US population level in older adults results in scenarios displaying increased healthcare resource utilization, that could compromise VCR. A better tolerability profile is needed for next generation, seasonal influenza vaccines.