Early resolution of retinal fluid after initiating faricimab therapy may help predict which patients with neovascular age-related macular degeneration can maintain extended treatment intervals, according to a post hoc analysis of the TENAYA and LUCERNE randomized clinical trials.
In the study, 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 suggested 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 III randomized, double-masked, multicenter trials comparing faricimab 6 mg administered up to every 16 weeks with aflibercept 2 mg given every 8 weeks in patients with treatment-naive neovascular age-related macular degeneration (nAMD). Previous results from the trials demonstrated that nearly 80% of the patients receiving faricimab were able to achieve treatment intervals of 12 weeks or longer by 2 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 the treatment intervals could be extended to every 8, 12, or 16 weeks. From week 60 onward, the patients entered a treat-and-extend phase 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, whereas 287 didn't achieve resolution. The patients with early fluid resolution were more likely to be assigned longer dosing intervals. Specifically, they had nearly twice the likelihood of receiving every-16-week dosing rather than every-8-week dosing and 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 a higher likelihood 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 the patients with early fluid resolution group compared with those whose retinal fluid persisted during the early treatment phase.
The investigators suggested that faricimab’s dual mechanism—simultaneously inhibition of 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 investigators cautioned that the findings should be interpreted carefully as a result of the post hoc nature of the analysis, they also noted that identifying early predictors of durability could help clinicians to better tailor treatment strategies and potentially reduce the injection burden among patients with nAMD.
Lead study author John D. Pitcher III, MD, of the Eye Associates of New Mexico, and colleagues concluded: "[T]he extended treatment durability seen with faricimab may help reduce the treatment burden on patients and health care systems" by freeing up clinical capacity currently being used to treat this patient population.
The research in this study was supported by F. Hoffmann-La Roche, including for third-party writing assistance, which was provided by Sofia Pedro, PhD, of Envision Pharma Group. Full disclosures can be found in the study.
Source: JAMA Ophthalmology
