Early resolution of retinal fluid after initiating faricimab therapy may help predict which patients with neovascular age-related macular degeneration (nAMD) can maintain extended treatment intervals, according to a post hoc analysis of the TENAYA and LUCERNE randomized clinical trials.
The investigators examined whether rapid drying of the retina – specifically the resolution of intraretinal fluid (IRF) and subretinal fluid (SRF) during the first 12 weeks of treatment – was associated with longer dosing intervals later in therapy. The findings suggest that early anatomical response may serve as a marker of treatment durability with the dual angiopoietin-2 (Ang-2) and vascular endothelial growth factor A (VEGF-A) inhibitor faricimab.
TENAYA and LUCERNE were phase 3 randomized, double-masked, multicenter trials comparing faricimab 6 mg administered up to every 16 weeks with aflibercept 2 mg given every eight weeks in patients with treatment-naïve nAMD. Previous results from the trials demonstrated that nearly 80% of patients receiving faricimab were able to achieve treatment intervals of 12 weeks or longer by two years while maintaining visual and anatomical outcomes.
The current analysis focused on participants assigned specifically to the faricimab arm. After four initial monthly injections through week 12, patients underwent disease-activity assessments at weeks 20 or 24 that determined whether treatment intervals could be extended to every 8, 12, or 16 weeks. From week 60 onward, patients entered a treat-and-extend regimen in which dosing intervals could be adjusted based on visual acuity, central subfield thickness, or other signs of disease activity.
Among 552 participants with available dosing data at week 20 or 24, 265 achieved resolution of IRF and SRF during the first 12 weeks of treatment, while 287 did not. Patients with early fluid resolution were significantly more likely to be assigned longer dosing intervals. Specifically, they had nearly twice the odds of receiving every-16-week dosing rather than every-8-week dosing and greater odds of receiving every-12-week dosing rather than every-8-week dosing.
A similar association was observed at the end of the study. Among 478 patients with available data at week 112, those who experienced early fluid resolution were more likely to remain on extended dosing intervals, and had higher odds of receiving every-16-week dosing compared with every-8-week dosing.
Visual outcomes also appeared comparable or slightly better among patients who experienced early fluid resolution. Mean best-corrected visual acuity at week 112 was numerically similar or higher in this group compared with patients whose retinal fluid persisted during the early treatment phase.
The researchers suggest that faricimab’s dual mechanism – simultaneously inhibiting Ang-2 and VEGF-A – may contribute to its rapid anatomical effects and extended durability. Early disease control reflected by fluid resolution could therefore represent an indicator of patients who are likely to sustain longer treatment intervals.
While the authors caution that these findings should be interpreted carefully due to the post hoc nature of the analysis, they also note that identifying early predictors of durability could help clinicians to better tailor treatment strategies and potentially reduce the injection burden for patients with nAMD. In turn, this would reduce the burden placed on healthcare systems by freeing up clinical capacity currently being used to treat these patients.
Source: JAMA Ophthalmology
The investigators examined whether rapid drying of the retina – specifically the resolution of intraretinal fluid (IRF) and subretinal fluid (SRF) during the first 12 weeks of treatment – was associated with longer dosing intervals later in therapy. The findings suggest that early anatomical response may serve as a marker of treatment durability with the dual angiopoietin-2 (Ang-2) and vascular endothelial growth factor A (VEGF-A) inhibitor faricimab.
TENAYA and LUCERNE were phase 3 randomized, double-masked, multicenter trials comparing faricimab 6 mg administered up to every 16 weeks with aflibercept 2 mg given every eight weeks in patients with treatment-naïve nAMD. Previous results from the trials demonstrated that nearly 80% of patients receiving faricimab were able to achieve treatment intervals of 12 weeks or longer by two years while maintaining visual and anatomical outcomes.
The current analysis focused on participants assigned specifically to the faricimab arm. After four initial monthly injections through week 12, patients underwent disease-activity assessments at weeks 20 or 24 that determined whether treatment intervals could be extended to every 8, 12, or 16 weeks. From week 60 onward, patients entered a treat-and-extend regimen in which dosing intervals could be adjusted based on visual acuity, central subfield thickness, or other signs of disease activity.
Among 552 participants with available dosing data at week 20 or 24, 265 achieved resolution of IRF and SRF during the first 12 weeks of treatment, while 287 did not. Patients with early fluid resolution were significantly more likely to be assigned longer dosing intervals. Specifically, they had nearly twice the odds of receiving every-16-week dosing rather than every-8-week dosing and greater odds of receiving every-12-week dosing rather than every-8-week dosing.
A similar association was observed at the end of the study. Among 478 patients with available data at week 112, those who experienced early fluid resolution were more likely to remain on extended dosing intervals, and had higher odds of receiving every-16-week dosing compared with every-8-week dosing.
Visual outcomes also appeared comparable or slightly better among patients who experienced early fluid resolution. Mean best-corrected visual acuity at week 112 was numerically similar or higher in this group compared with patients whose retinal fluid persisted during the early treatment phase.
The researchers suggest that faricimab’s dual mechanism – simultaneously inhibiting Ang-2 and VEGF-A – may contribute to its rapid anatomical effects and extended durability. Early disease control reflected by fluid resolution could therefore represent an indicator of patients who are likely to sustain longer treatment intervals.
While the authors caution that these findings should be interpreted carefully due to the post hoc nature of the analysis, they also note that identifying early predictors of durability could help clinicians to better tailor treatment strategies and potentially reduce the injection burden for patients with nAMD. In turn, this would reduce the burden placed on healthcare systems by freeing up clinical capacity currently being used to treat these patients.
Source: JAMA Ophthalmology
