Systemic counterregulatory response of angiopoietin-2 after intravitreal injections with faricimab for nAMD.

Purpose: Recently, a systemic counterregulatory response of angiopoietin-2 after intravitreal application of the anti vascular endothelial growth factor (anti-VEGF) drug aflibercept in neovascular age-related macular degeneration (nAMD) has been described. The aim of the study was to find out wether faricimab, a combined anti-VEGF/angiopoietin-2 drug, had an effect on systemic cytokine levels.

Methods: 20 women and 11 men (mean age 79.5 ± 7.3 years) were included into this cohort study. Plama levels of VEGF-A and angiopoietin-2 were determined before and after intravitreal application of faricimab (6 mg/0.05 ml/eye) using ELISA-technique. These results were correlated with central macular thickness (CMT). Responders were defined as having had CMT thinning ≥ 50 μm.

Results: CMT decreased from 384.8 ± 108.8 μm prior to intravitreal injection (IVI) to 286.1 ± 63 μm one month after IVI (p < 0.0001). Angiopoietin-2 levels increased from 526.9 ± 129 pg/ml to 597.2 ± 174.8 pg/ml (p = 0.0087) one week after IVI and dropped to 547.4 ± 165 pg/ml (ns) four weeks after IVI. Responders revealed higher angiopoietin-2 (p = 0.0035) as well as higher VEGF-A (p = 0.0248) levels throughout the study period compared to non-responders. Initial CMT revealed to be the only independent factor influencing CMT 4 weeks after IVI in linear regression models with a positive correlation between initial thickness and effect size.

Conclusion: The trending increase in systemic angiopoietin-2 levels, may be interpreted as an escape mechanism of the concomitant anti-VEGF component of therapy. Angiopoietin-2 levels could serve as a positive predictive factor of therapy response in the future. Further research regarding this effect as well as differences between responders and non-responders is mandatory.

Key messages: What is known Bispecific antibodies may be more beneficial compared to monospecific antibodies in neovascular age related macular degeneration (nAMD). For monospecific antibodies, there are systemic effects on systemic vascular endothelial growth factor (VEGF) levels. What is new The knew bispecific antibody faricimab entails an increase in systemic angiopoietin-2 levels, as well as a decrease in VEGF levels. The increase in systemic angiopoietin-2 may be interpreted as a counterregulatory effect. The decrease in systemic VEGF levels resembles the effects of monospecific antibodies.