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J Med Econ
. 2026 Dec;29(1):2046-2062.
doi: 10.1080/13696998.2026.2706361. Epub 2026 Aug 4.
Indirect comparison of mRNA-1010 versus enhanced influenza vaccines in adults aged 65 years and older during the 2024-2025 US influenza season
Keya Joshi 1 , Aaron Situ 1 2 , Darshan Mehta 1 , Linwei Li 1 , Chelsea Canan 1 , John Youhanna 1 , Jennifer M Radin 1 , Deborah Rudin 1 , Mihaela Georgieva 1 , Nicolas Van de Velde 1
Affiliations
Aims: 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.
Materials and methods: 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.
Results: 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.
Limitations and conclusions: 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.
Keywords: C10; I10; I18; indirect treatment comparison; influenza; older adults; relative vaccine effectiveness; vaccines.
. 2026 Dec;29(1):2046-2062.
doi: 10.1080/13696998.2026.2706361. Epub 2026 Aug 4.
Indirect comparison of mRNA-1010 versus enhanced influenza vaccines in adults aged 65 years and older during the 2024-2025 US influenza season
Keya Joshi 1 , Aaron Situ 1 2 , Darshan Mehta 1 , Linwei Li 1 , Chelsea Canan 1 , John Youhanna 1 , Jennifer M Radin 1 , Deborah Rudin 1 , Mihaela Georgieva 1 , Nicolas Van de Velde 1
Affiliations
- PMID: 42550058
- DOI: 10.1080/13696998.2026.2706361
Aims: 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.
Materials and methods: 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.
Results: 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.
Limitations and conclusions: 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.
Keywords: C10; I10; I18; indirect treatment comparison; influenza; older adults; relative vaccine effectiveness; vaccines.