Rapid Fluid Resolution and Faricimab Durability in nAMD: TENAYA/LUCERNE Post Hoc Findings

In nAMD trials that use interval-assignment algorithms, a recurring question is whether early “drying” on optical coherence tomography relates to later dosing durability. In a post hoc analysis of treatment-naive nAMD participants treated with faricimab in TENAYA and LUCERNE, the authors examined whether absence of both intraretinal fluid (IRF) and subretinal fluid (SRF) through week 12 was associated with longer dosing intervals later in the study. Interval assignment was evaluated at the first extension opportunity (week 20 or 24, per protocol) and again at study completion (week 112). The study frames early anatomic fluid resolution as a potential durability signal within the trials’ interval-assignment framework.

In the faricimab-treated cohort, fluid resolution through week 12 was defined as absence of both IRF and SRF at weeks 4, 8, and 12 among participants who had IRF or SRF at baseline. Week-12 combined IRF+SRF resolution status served as the predictor, and outcomes were dosing-interval categories (every 8, 12, or 16 weeks) at week 20/24 and at week 112. The authors report 552 participants with interval data at week 20/24 (265 with week-12 IRF+SRF resolution and 287 without) and 478 with interval data at week 112 (223 with resolution and 255 without). Analyses used adjusted multinomial logistic regression, reported as odds of longer intervals relative to every-8-week dosing.

At week 20/24, the authors report higher adjusted odds of being assigned every-16-week vs every-8-week dosing among participants with week-12 IRF+SRF resolution (OR, 1.99; 95% CI, 1.23–3.21; P = .005), as well as higher adjusted odds of every-12-week vs every-8-week dosing (OR, 1.77; 95% CI, 1.09–2.87; P = .02). By week 112, they report higher adjusted odds of every-16-week vs every-8-week dosing (OR, 1.76; 95% CI, 1.10–2.83; P = .02), while the every-12-week vs every-8-week comparison had an OR of 1.65 (95% CI, 0.89–3.05; P = .11). The study notes that P values were nominal and unadjusted for multiplicity, and that no formal statistical conclusions should be made based on P values alone. These estimates are presented in the article as evidence linking early fluid status during faricimab loading to later interval assignment, with the strongest signal in the every-16-week contrasts at both time points.

The authors also describe a covariate selection process that yielded different final multivariable model compositions at the two evaluation points. For the week 20/24 model, the final adjusted analysis included baseline maximum pigment epithelial detachment (PED) thickness and choroidal neovascularization (CNV) lesion location. For the week 112 model, the final adjusted analysis included baseline maximum PED thickness and total lesion size. The article presents these baseline anatomic and lesion characteristics as the variables retained in the final adjusted models.

In the discussion, the authors interpret the findings as suggesting that rapid fluid resolution through week 12 may serve as a predictor of extended durability—defined in this context as assignment to dosing every 12 weeks or longer—within the TENAYA/LUCERNE trial framework. They also emphasize limitations, including the post hoc design. The article further notes that dosing-interval assignment was protocol-defined based on disease activity assessments at week 20/24 and later treat-and-extend criteria, which the authors present as important context when interpreting associations between early anatomic response and later interval categories. Early anatomic response is positioned as associated with, but not determinative of, later interval assignment.

Key Takeaways:

• The authors report an association between week-12 combined IRF+SRF resolution and later dosing-interval assignment (every 8, 12, or 16 weeks) at week 20/24 and week 112.
• Adjusted analyses were reported to show higher odds of longer intervals overall, with a clearer signal for every-16-week dosing and mixed evidence for every-12-week dosing at week 112.
• Limitations noted by the authors include the post hoc design and the role of protocol-defined interval-assignment criteria in shaping later interval categories.