Elicit: Clinical Outcomes of Aflibercept in AMD and DME

Clinical Outcomes of Aflibercept in AMD and DME

What clinical outcomes support aflibercept treatment of wet AMD and diabetic macular edema?

Aflibercept treatment for wet AMD and diabetic macular edema is supported by visual acuity improvements equivalent to ranibizumab and superior to laser photocoagulation, significant anatomical improvements including central retinal thickness reductions and diabetic retinopathy severity improvements, clinically meaningful quality of life gains, and a safety profile comparable to other anti-VEGF agents with the advantage of less frequent dosing.

Abstract

Aflibercept treatment for wet age-related macular degeneration produces visual acuity outcomes equivalent to ranibizumab, with both treatments showing similar mean BCVA changes (within 0.5 letters) and approximately 32% of patients gaining ≥15 letters at one year. Anatomical outcomes were also similar, with comparable proportions achieving dry retina (RR 1.06, 95% CI 0.98 to 1.14) and equivalent choroidal neovascularization area reductions. For diabetic macular edema, aflibercept demonstrated statistically significant superiority over laser photocoagulation, with mean BCVA gains of 10.5-13.6 letters compared to -0.5 to 1.2 letters for laser (p<0.0001), and central retinal thickness reductions of 183-195 μm versus 66-73 μm for laser (p<0.0001). At 148 weeks, 35.8-42.9% of aflibercept-treated eyes gained ≥15 letters versus 13.6-18.9% with laser. Aflibercept showed non-inferiority to bevacizumab (mean improvement 15.0 versus 14.0 letters, p=0.37) and better anatomical outcomes than ranibizumab in real-world practice (central subfield thickness reduction -114.4 μm versus -87.8 μm, p<0.01). Quality of life improved meaningfully in both conditions, with NEI VFQ-25 total score gains of +6.11 points in DME and clinically significant improvements across multiple subscales in wet AMD. The safety profile was comparable to other anti-VEGF agents, with serious systemic adverse events similar to ranibizumab (RR 0.99, 95% CI 0.79 to 1.25) and no new safety signals identified in long-term use. The every-8-weeks maintenance dosing regimen after initial loading reduced treatment burden compared to monthly regimens while maintaining efficacy.

Methods

We analyzed 10 sources from an initial pool of 200, using 8 screening criteria. Each paper was reviewed for 8 key aspects that mattered most to the research question.

Screening

We screened in sources based on their abstracts that met these criteria:

Results

Characteristics of included studies

The systematic review included 10 sources examining aflibercept treatment for wet AMD and DME. These comprised randomized controlled trials, observational studies, and systematic reviews.

Study Study Type Sample Size Patient Population Comparator Follow-up Duration
J. Heier et al., 2012 RCT 2419 patients Wet AMD Ranibizumab 52 weeks
J. M. Ruiz-Moreno, 2015 Phase III RCT 461/402 patients DME Laser 52 weeks
J. Heier et al., 2016 Phase III RCT 872 eyes DME Laser 148 weeks
Chirag Jhaveri et al., 2022 RCT 312 eyes (158 aflibercept) DME Bevacizumab first 2 years
You-Xin Chen et al., 2020 Phase III RCT 127 eyes per group DME Laser 52 weeks
Pierre-Henry Gabrielle et al., 2022 Retrospective 534 eyes (267 aflibercept) DME Ranibizumab 3 years
S. Sarwar et al., 2016 Cochrane review 2457 participants Wet AMD Ranibizumab 1-2 years
J. Carrasco et al., 2021 Meta-analysis 40-2506 patients/eyes Wet AMD None 2 years
M. Yuzawa et al., 2015 Phase III RCT 2419 patients (607 aflibercept) Wet AMD Ranibizumab 52 weeks
J. Garweg et al., 2019 Phase IV single-arm 553 patients DME None 52 weeks

The studies represented diverse designs, with five focusing on wet AMD and five on DME. Most studies were randomized controlled trials with comparators including ranibizumab and laser photocoagulation.

Visual Acuity Outcomes

Aflibercept demonstrated substantial and sustained visual acuity improvements in wet AMD across multiple studies. In the VIEW trials comparing aflibercept to ranibizumab, all aflibercept regimens were within 0.5 letters of ranibizumab for mean change in BCVA, demonstrating clinical equivalence. At one year, the mean change in BCVA was similar between aflibercept and ranibizumab groups.

Study Time Point Mean BCVA Change Proportion Gaining ≥15 Letters Statistical Significance
S. Sarwar et al., 2016 1 year -0.15 letters ~32% High-quality evidence
S. Sarwar et al., 2016 2 years 7.2 letters ~31% High-quality evidence
J. Carrasco et al., 2021 2 years +4.49 letters Not reported Not specified
M. Yuzawa et al., 2015 52 weeks Similar improvements Not reported Similar to ranibizumab

Anatomical Outcomes

Aflibercept produced significant anatomical improvements in both wet AMD and DME.

Study Time Point Aflibercept CRT Change Comparator CRT Change p-value
J. M. Ruiz-Moreno, 2015 52 weeks -185.9 μm -73.3 μm (laser) p<0.0001
You-Xin Chen et al., 2020 52 weeks Significantly greater Laser Not specified
Pierre-Henry Gabrielle et al., 2022 3 years -114.4 μm -87.8 μm p<0.01

Quality of Life

Quality of life assessments demonstrated clinically meaningful improvements with aflibercept treatment in both wet AMD and DME, reinforcing its use in these conditions. Specifically, NEI VFQ-25 scores indicated significant improvements after treatment.

Safety Profile

The safety profile of aflibercept was favorable and comparable to other anti-VEGF agents, showing similar rates of serious ocular adverse events and treatment-emergent adverse events across different studies. No new safety signals were identified in long-term use.

Conclusion

Overall, aflibercept demonstrates effective outcomes in treating wet AMD and diabetic macular edema, with a beneficial safety profile and the advantage of less frequent dosing, making it a viable treatment option.