Indirect comparison of mRNA-1010 versus enhanced influenza vaccines in adults aged 65 years and older during the 2024-2025 US influenza season.
Seasonal influenza continues to cause severe disease among older adults in the United States despite enhanced vaccine recommendations, driven by immunosenescence and vaccine mismatch with circulating influenza viruses. mRNA-based influenza vaccines (mRNA-1010), addressing some of these challenges, have been developed for this population. A previous trial found mRNA-1010 demonstrated superior immunogenicity compared to enhanced high-dose influenza vaccination. As no direct evidence exists comparing mRNA-1010 efficacy to currently available enhanced influenza vaccines (EVs), we aimed to indirectly compare the effectiveness of mRNA-1010 and licensed EVs against medically attended influenza infection among adults ≥65 years in the US.
We conducted an anchored indirect treatment comparison (ITC) using the Bucher method to estimate the relative vaccine effectiveness (rVE) of mRNA-1010 vs EV, with standard-dose egg-based influenza vaccine as the anchor, using individual patient-level data from adults ≥65 years from a real-world Optum claims-based analysis and the pivotal mRNA-1010-P304 clinical trial. Target trial emulation and inverse probability weighting (IPW) were implemented to address potential bias due to cross-population differences. Sensitivity analyses were conducted using alternative outcome definition, alternative weighting approaches and US trial sites only.
Assessments of post-IPW supported a comparable common anchor for the ITC. Among adults ≥65 years, the indirect rVE of mRNA-1010 vs. enhanced vaccines against medically attended influenza was 12.82% (95% CI: -36.91%, 44.49%). Sensitivity analyses also supported these findings.
mRNA-1010, a new mRNA-based influenza vaccine, was shown to be comparable to currently licensed EVs among older adults ≥65 years against medically attended influenza outcomes. Consistency of findings across sensitivity analyses support the robustness of these results. Newer influenza vaccine modalities, including mRNA-based vaccines provide an additional comparable option to existing EVs to help further reduce severe influenza disease burden among older adults ≥65 years for whom enhanced vaccines are recommended.
We conducted an anchored indirect treatment comparison (ITC) using the Bucher method to estimate the relative vaccine effectiveness (rVE) of mRNA-1010 vs EV, with standard-dose egg-based influenza vaccine as the anchor, using individual patient-level data from adults ≥65 years from a real-world Optum claims-based analysis and the pivotal mRNA-1010-P304 clinical trial. Target trial emulation and inverse probability weighting (IPW) were implemented to address potential bias due to cross-population differences. Sensitivity analyses were conducted using alternative outcome definition, alternative weighting approaches and US trial sites only.
Assessments of post-IPW supported a comparable common anchor for the ITC. Among adults ≥65 years, the indirect rVE of mRNA-1010 vs. enhanced vaccines against medically attended influenza was 12.82% (95% CI: -36.91%, 44.49%). Sensitivity analyses also supported these findings.
mRNA-1010, a new mRNA-based influenza vaccine, was shown to be comparable to currently licensed EVs among older adults ≥65 years against medically attended influenza outcomes. Consistency of findings across sensitivity analyses support the robustness of these results. Newer influenza vaccine modalities, including mRNA-based vaccines provide an additional comparable option to existing EVs to help further reduce severe influenza disease burden among older adults ≥65 years for whom enhanced vaccines are recommended.
Authors
Joshi Joshi, Situ Situ, Mehta Mehta, Li Li, Canan Canan, Youhanna Youhanna, Radin Radin, Rudin Rudin, Georgieva Georgieva, Van de Velde Van de Velde
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