The advent of faricimab, the first bispecific antibody targeting both vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2), has opened new avenues for treating neovascular age-related macular degeneration (nAMD). A recent study has revealed significant changes in the cytokine profile of aqueous humor following intravitreal injection of faricimab, providing insights on treatment effectiveness and resistance factors.
This prospective observational case series, conducted at the Ophthalmology Department of Nagoya University Hospital, focused on treatment-naïve patients with nAMD. A total of 32 participants were enrolled, and their cytokine levels, particularly VEGF-A, Ang-2, and placental growth factor (PlGF), were measured before and after faricimab treatment.
Neovascular age-related macular degeneration is known for causing severe vision loss due to abnormal growth of blood vessels under the retina. Anti-VEGF therapies, like ranibizumab and aflibercept, have been standard treatments; yet, there are challenges concerning long-term efficacy and treatment adherence. Faricimab, introduced for its dual-action capability, was expected to address some of these issues.
Before the administration of faricimab, the mean corrected visual acuity (BCVA) was 0.37 ± 0.24. After treatment, BCVA showed no significant change at one month, recording 0.34 ± 0.26 (P = 0.28). Conversely, the study indicated significant reductions in mean central retinal thickness (CRT), decreasing from 391.9 ± 222.4 μm to 288.8 ± 107.0 μm, representing approximately 73.7% reduction (P < 0.01).
When analyzing exudative changes using optical coherence tomography (OCT), over 90% of the treated eyes exhibited improvement one month post-injection. Specifically, 25% of the eyes displayed complete absorption of exudative changes, marking the effectiveness of faricimab in managing this debilitating condition.
One key finding from the study was the change in cytokine levels. At baseline, models revealed mean Ang-2 concentrations of 6.35 ± 6.39 pg/mL, which dropped significantly to 2.94 ± 5.04 pg/mL post-treatment (P < 0.01). PlGF levels followed suit, with initial concentrations of 1.22 ± 2.89 pg/mL decreasing to 0.92 ± 2.28 pg/mL (P < 0.01). Perhaps most significantly, the VEGF-A concentration was observed to decrease below the detectable limit post-treatment.
The results of the study identified 19 eyes (59.4%) as responders to faricimab based on CRT reductions exceeding 30 µm when comparing baseline measurements. Responders demonstrated higher baseline CRT and Ang-2 concentrations compared to non-responders, implying Ang-2's potential as both a biomarker of response and treatment efficacy.
The role of Ang-2 is particularly interesting because it plays both sides when it pertains to vascular stability and permeability. Under normal circumstances, Ang-1 promotes vessel stabilization; when Ang-2 is elevated, it counteracts this effect, leading to increased vascular instability often observed within nAMD pathology.
Overall trends indicated no significant difference across nAMD subtypes for aqueous humor cytokine levels, reinforcing Ang-2's unique importance as it consistently correlated with treatment response. Interestingly, factors such as central choroidal thickness and other demographic characteristics exhibited no significant variation related to the treatment dispositional differences.
Through this analysis, faricimab has demonstrated compelling effects on altering cytokine levels associated with exudative changes. The concurrent decrease of VEGF and Ang-2 suggests successful multi-targeted therapy aimed to stabilize ocular vasculature, improving clinical outcomes for patients suffering from nAMD. Future studies, especially those with larger cohorts and extended treatment timelines, are necessary to develop comprehensive insights about the long-term efficacy of faricimab and the mechanistic roles of cytokines.
The findings from this study illuminate advances toward improving nAMD treatment protocols incorporating faricimab, emphasizing the necessity for continuous evaluation of cytokine levels to refine therapeutic strategies and predict patient responses effectively.
These pivotal results will significantly impact clinical practices and potentially guide future research, affirming faricimab as more than just another therapy but potentially, through enhanced biomarkers and improved treatment plans, step closer to the ultimate goal of eradicative therapy for AMD.