Faricimab 6 mg Versus Aflibercept 8 mg in Treatment-Naïve Neovascular Age-Related Macular Degeneration: A Protocol-Standardised In Silico Study

Background: Faricimab 6 mg and aflibercept 8 mg permit extended treatment intervals in neovascular age-related macular degeneration (nAMD), but their pivotal programmes used different loading and maintenance schedules. This study compared treatment burden under the same loading and treat-and-extend protocol and included an exploratory longitudinal analysis of published aggregate visual and anatomical outcomes. Methods: Treatment-specific Dirichlet distributions represented persistent Q8W, Q12W and Q16W capability. Both treatments received injections at weeks 0, 4, 8 and 16, followed by identical four-week extensions from Q8W to Q16W. The primary analysis comprised 30,000 evidence draws, 100,000 paired virtual eyes, a 1.5-million-pair scenario grid and a nested five-million-pair probabilistic analysis. Exploratory multilevel meta-regressions estimated BCVA and change in retinal thickness through week 52; IRF, SRF and complete retinal dryness were analysed separately. Results: Mean injections with faricimab and aflibercept 8 mg were 7.255 and 7.212 at week 52 and 11.522 and 11.144 at week 104. The nested 104-week difference was −0.393 injection (95% uncertainty interval −0.682 to −0.107), but broad source-weight uncertainty included no difference and credible source analyses changed the direction of the contrast. Exploratory week-52 BCVA gains were 5.65 and 6.29 letters, respectively; the difference was 0.64 letter (95% uncertainty interval −1.41 to 2.70) and should be interpreted in the context of three aflibercept 8 mg study families. The expanded retinal-thickness sensitivity model estimated changes of −171.8 and −147.2 micrometres, while the between-treatment direction varied in the three-dose-only analysis. Complete retinal dryness was projected in 57.0% and 69.0% of eyes, respectively, based on three study families per treatment. Conclusions: Use of the same protocol predicted essentially equal one-year burden and a small two-year fixed-weight difference that varied across source choices. The exploratory longitudinal projections, informed by three independent aflibercept 8 mg study families at one year, provide supportive context for the visual and anatomical findings but should be interpreted as hypothesis-generating rather than confirmatory.