A model to quantify the influence of treatment patterns and optimize outcomes in nAMD

Abstract

Neovascular age-related macular degeneration (nAMD) is a progressive retinal disease that often leads to severe and permanent vision loss. Early initiation of anti-vascular endothelial growth factor (anti-VEGF) therapy has been shown to preserve vision in nAMD patients. Concurrently, treatment outcomes in real-world are inferior to those reported in clinical trials. The most likely reasons observed are fewer treatment-intensity in routine clinical practice than in clinical trials. The other possibility could be the delay in starting treatment and the re-treatment interval. Although a negative impact of aforementioned parameters seems obvious, quantitative impact measures remain elusive in a real-world setting due to a lack of an ‘optimal treatment’ control group. To overcome this shortcoming, we developed, validated, and applied a model to assess and quantify the impact of anti-VEGF administration variables on visual acuity development in a prospective nAMD patient cohort. The model was further applied to probe the impact of the COVID-19 pandemic on visual progressions in nAMD patients. The presented model paves the way to systematically explore and evaluate realistic interventions in the current treatment paradigm, that can be adopted in routine clinical care.

Comparative Efficacy of Brolucizumab in the Treatment of Neovascular Age-Related Macular Degeneration: A Systematic Literature Review and Network Meta-Analysis

“…Patients with nAMD demonstrate high individual variability in the need for anti-VEGF injections. Delay in initiating treatment as well as undertreatment caused by poor adherence and/or persistence leads to worsening treatment outcomes over time [ 6 – 8 ]. Differing treatment regimens have been shown to impact treatment adherence and persistence, with treat and extend or comparable regimens fairing best.…”

Review on the Safety and Efficacy of Brolucizumab for Neovascular Age-Related Macular Degeneration From Major Studies and Real-World Data

“…6,7 However, poor adherence to treatment due to the need for frequent injections, delay in initiating treatment, undertreatment, patient dissatisfaction, as well as the burden of treatments may all contribute to suboptimal or even progressively worse visual outcomes. [8][9][10][11][12] Brolucizumab (Beovu; Novartis) is a humanized, singlechain variable fragment antibody acting against VEGF-A with a very low molecular mass of ~26 kDa that inhibits all isoforms of VEGF-A and is approved for use in nAMD and diabetic macular edema (DME) by the US Food and Drug Admin-istration (FDA) on October 8, 2019 and June 1, 2022, respectively. 13 A single-chain variable fragment is an autonomous binding agent independent of a heavy molecular support structure despite retaining its total binding capacity to the target.…”

“…Prompt treatment with monotherapy using anti-VEGF agents has been shown to limit vision loss in about 95% of people with nAMD 6,7. However, poor adherence to treatment due to the need for frequent injections, delay in initiating treatment, undertreatment, patient dissatisfaction, as well as the burden of treatments may all contribute to suboptimal or even progressively worse visual outcomes 8–12…”

Phase I DAVIO Trial: EYP-1901 Bioerodible, Sustained-Delivery Vorolanib Insert in Patients With Wet Age-Related Macular Degeneration

“… 13 , 14 Achieving efficacy with anti-VEGF treatment in wAMD is often accomplished with a high frequency of injections, typically ranging from 1 to 4 months. 15 , 16 Adherence to a rigid intravitreal schedule is challenging, and some physicians opt for a pro re nata or treat-and-extend approach to ease the treatment and visit burden while maintaining treatment benefits, usually measured by visual acuity and anatomic response on OCT. 15 However, adherence to treatment visits is still a challenge, as demonstrated by undertreatment with anti-VEGF therapies across patients with wAMD. 14 Some patients with wAMD discontinue treatment and this is associated with poor visual outcomes.…”