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.

Paper search

We performed a semantic search across over 138 million academic papers from the Elicit search engine, which includes all of Semantic Scholar and OpenAlex.

We ran this query: “What clinical outcomes support aflibercept treatment of wet AMD and diabetic macular edema?”

The search returned 200 total results from Elicit. We retrieved 200 papers most relevant to the query for screening.

Results

Characteristics of included studies

The systematic review included 10 sources examining aflibercept treatment for wet age-related macular degeneration (AMD) and diabetic macular edema (DME). These comprised randomized controlled trials, observational studies, and systematic reviews.

Study Full text retrieved? Study Type Sample Size Patient Population Baseline Characteristics Comparator Follow-up Duration
J. Heier et al., 2012 Yes RCT 2419 patients Wet AMD Active, subfoveal CNV Ranibizumab 52 weeks
J. M. Ruiz-Moreno, 2015 No Phase III RCT 461/402 patients DME Not specified Laser 52 weeks
J. Heier et al., 2016 No Phase III RCT 872 eyes DME Central-involved DME Laser 148 weeks
Chirag Jhaveri et al., 2022 No RCT 312 eyes (158 aflibercept) DME Moderate vision loss (VA 24-69 letters) Bevacizumab first 2 years
You-Xin Chen et al., 2020 No Phase III RCT 127 eyes per group DME Not specified Laser 52 weeks
Pierre-Henry Gabrielle et al., 2022 No Retrospective 534 eyes (267 aflibercept) DME Moderate (VA ≤68) and mild (VA ≥69) impairment Ranibizumab 3 years
S. Sarwar et al., 2016 No Cochrane review 2457 participants Wet AMD Treatment-naive, active subfoveal CNV Ranibizumab 1-2 years
J. Carrasco et al., 2021 Yes Meta-analysis 40-2506 patients/eyes Wet AMD Mean age 78.62 years, baseline BCVA 57.73 letters None 2 years
M. Yuzawa et al., 2015 No Phase III RCT 2419 patients (607 aflibercept) Wet AMD Treatment-naive, exudative AMD Ranibizumab 52 weeks
J. Garweg et al., 2019 No Phase IV single-arm 553 patients DME Mean BCVA 61.5 letters, mean CRT 464.81 μm 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, bevacizumab, and laser photocoagulation. Follow-up durations ranged from 52 weeks to 3 years. Only two studies had full texts available for detailed extraction.

Effects

Visual Acuity Outcomes in Wet AMD

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 (mean difference -0.15 ETDRS letters, 95% CI -1.47 to 1.17). This similarity persisted at two years.

Study Time Point Mean BCVA Change Proportion Gaining ≥15 Letters Proportion Achieving ≥70 Letters Statistical Significance
S. Sarwar et al., 2016 1 year -0.15 letters vs ranibizumab (95% CI -1.47 to 1.17) ~32% (RR 0.97, 95% CI 0.85 to 1.11) Not reported High-quality evidence
S. Sarwar et al., 2016 2 years 7.2 letters ~31% (RR 0.98, 95% CI 0.85 to 1.12) Not reported High-quality evidence
J. Carrasco et al., 2021 2 years +4.49 letters Not reported 47.39% Not specified
M. Yuzawa et al., 2015 52 weeks Similar improvements in NEI VFQ-25 Not reported Not reported Similar to ranibizumab

The real-world meta-analysis reported a mean BCVA of 62.55 ETDRS letters at 2 years, with 47.39% of patients achieving visual acuity of ≥70 letters.

Visual Acuity Outcomes in Diabetic Macular Edema

Aflibercept demonstrated consistent superiority over laser photocoagulation and non-inferiority to other anti-VEGF agents in DME.

Study Time Point Aflibercept Regimen Mean BCVA Gain Proportion Gaining ≥15 Letters Comparator BCVA Gain p-value
J. M. Ruiz-Moreno, 2015 52 weeks 2q4 (VISTA) 12.5 letters Significant vs laser 0.2 letters (laser) p<0.0001
J. M. Ruiz-Moreno, 2015 52 weeks 2q8 (VISTA) 10.7 letters Significant vs laser 0.2 letters (laser) p<0.0001
J. M. Ruiz-Moreno, 2015 52 weeks 2q4 (VIVID) 10.5 letters Significant vs laser 1.2 letters (laser) p<0.0001
J. Heier et al., 2016 148 weeks 2q4 (VISTA) 10.4 letters 42.9% 1.4 letters (laser) p<0.0001
You-Xin Chen et al., 2020 52 weeks 2q4 +13.6 letters 43.3% -0.5 letters (laser) p<0.0001

Long-term outcomes remained robust. At 148 weeks, mean BCVA gains with aflibercept were significantly higher than laser control. The proportion of eyes gaining ≥15 letters at 148 weeks ranged from 35.8% to 42.9% for aflibercept versus 13.6% to 18.9% for laser control.

Anatomical Outcomes

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

Study Time Point Aflibercept CRT Change (2q4) Aflibercept CRT Change (2q8) Comparator CRT Change p-value
J. M. Ruiz-Moreno, 2015 52 weeks (VISTA) -185.9 μm -183.1 μm -73.3 μm (laser) p<0.0001
J. M. Ruiz-Moreno, 2015 52 weeks (VIVID) -195.0 μm -192.4 μm -66.2 μm (laser) p<0.0001
Pierre-Henry Gabrielle et al., 2022 3 years N/A -114.4 μm (95% CI -134.4 to -94.3) -87.8 μm (ranibizumab) p<0.01

The real-world comparison to ranibizumab showed aflibercept had significantly better anatomical outcomes.

Vision-Related Quality of Life

Quality of life assessments demonstrated clinically meaningful improvements with aflibercept treatment.

Quality of Life Measure Baseline Score Week 52 Change Clinical Significance
NEI VFQ-25 total score 70.12 +6.11 (SD 11.46) Clinically meaningful
Near activities subscale Not specified +11.37 (SD 18.01) More pronounced than distance
Distance activities subscale Not specified +7.33 (SD 17.32) Clinically meaningful
Better-seeing eye Not specified +7.74 (SD 13.59) Comprehensive improvement
Worse-seeing eye Not specified +5.48 (SD 9.70) Clinically meaningful

Safety Profile

The safety profile of aflibercept was generally favorable. Serious systemic adverse events were similar between aflibercept and ranibizumab (RR 0.99, 95% CI 0.79 to 1.25), while the risk of serious ocular adverse events was lower in the aflibercept group (RR 0.62, 95% CI 0.36 to 1.07).

Study Serious Ocular Adverse Events Treatment-Emergent Adverse Events Deaths Safety Conclusion
J. M. Ruiz-Moreno, 2015 Similar across groups Similar ocular and nonocular events Not reported Comparable to laser
J. Heier et al., 2016 Cataract: 3.1% Consistent with known profile Not reported Known safety profile maintained
J. Garweg et al., 2019 Endophthalmitis (0.5%) 53.6% overall; 26.8% ocular 5 (0.9%), not treatment-related Consistent with known profile

Treatment Regimens

Aflibercept was administered at a dose of 2 mg across all studies. Two primary dosing regimens emerged:

The eight-week dosing regimen represented reduced treatment requirements compared to monthly dosing regimens.

Comparative Effectiveness

Aflibercept demonstrated non-inferiority to ranibizumab in wet AMD and superiority to laser photocoagulation in DME, while showing comparable effectiveness to bevacizumab.

References