Evaluating the effect of ranibizumab and aflibercept on systemic vascular endothelial growth factor levels in neovascular age-related macular degeneration: the UNRAVEL study

Abstract

Purpose : UNRAVEL (NCT01988662) was the first large randomized clinical study specifically designed to assess the effect of intravitreal ranibizumab (RBZ) and aflibercept (AFL) on plasma free vascular endothelial growth factor (VEGF) levels in treatment-naïve patients with neovascular age-related macular degeneration (nAMD).

Methods : This Phase IV, parallel-group, patient-and rater-blinded, single-cohort, comparative study was conducted across 7 countries. Patients (N=205) aged ≥50 years with newly diagnosed active choroidal neovascularization secondary to AMD were randomized (1:1) to receive 3 monthly injections of either RBZ 0.5 mg (n=104) or AFL 2.0 mg (n=101). The primary endpoint was the percent reduction in plasma free VEGF-A levels at Month 3 versus baseline. VEGF-A levels were determined by a quantitative sandwich immunoassay in Citrate-Theophylline-Adenosine-Dipyridamole (CTAD) plasma. Statistical analysis was performed using a mixed model repeated measures analysis.

Results : Overall, 199 patients (100 RBZ; 99 AFL) completed the study and baseline characteristics were similar between the treatment groups. With AFL, mean plasma VEGF-A levels reduced from a pretreatment baseline of 31.0 pg/mL to 12.4 pg/mL at Month 3; with RBZ the levels remained similar at both timepoints, 29.1 mg/mL and 28.1 pg/mL, respectively (Figure A). A statistically significant percent reduction in plasma free VEGF-A levels from baseline was observed at Month 3 with AFL versus RBZ (least square mean difference point estimate [95% confidence interval]: 62.57 [13.96; 111.17], p=0.012; Figure B). A weak positive correlation (p<0.05) between percent reduction in plasma VEGF-A levels and serum anti-VEGF concentration was observed at Week 1 and Month 3 with AFL. The efficacy outcomes were similar between treatment groups; reported adverse events were consistent with the known safety profile of each drug.

Conclusions : At Month 3, AFL led to a statistically significant 2.5-fold greater percent reduction in plasma free VEGF-A levels versus RBZ in treatment-naïve patients with nAMD.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

Figure A: Mean plasma VEGF-A levels from baseline to Month 3

 

Figure B: Percent change from baseline in plasma VEGF-A levels at Month 3