Efficacy of Intravitreal Aflibercept Administered using Treat-and-Extend Regimen over 2 Years in Patients with Neovascular Age-Related Macular Degeneration: 1-Year ARIES Results.

Abstract

Purpose : To assess whether intravitreal aflibercept injection (IAI) administered in an early treat-and-extend (T&E) regimen is noninferior to a late-start T&E regimen in neovascular age-related macular degeneration (nAMD).

Methods : ARIES (NCT02581891) is a multicentre, randomised, open-label, active-controlled, parallel-group, Phase 3b/4 study comparing the efficacy of IAI administered by 2 different T&E regimens over 2 years in treatment-naïve patients with nAMD. All patients received 3 initial monthly doses of IAI (Weeks 0, 4, and 8), followed by an injection at an 8-week treatment interval (Week 16). At Week 16, patients were randomised 1:1 to an early-start T&E arm (T&E regimen extended by 2 weeks or an initial 4-week interval [maximum 16 weeks]) or a late-start T&E arm (2 mg IAI every 8 weeks [2q8] until Week 52, followed by T&E). Primary endpoint is change in best-corrected visual acuity (BCVA) from randomisation (Week 16) to Week 104. Interim results at Week 52 are presented here.

Results : A total of 287 treatment-naïve patients with nAMD were enrolled. At Week 16, 271 patients were randomised to an early-start T&E or fixed 2q8 regimen. Baseline characteristics were largely similar between treatment arms. At Week 52, absolute BCVA letter score change (67.6 vs 68.3 ETDRS letters), from randomisation (+0.9 vs +1.1 ETDRS letter difference), and mean number of injections (7.2 vs 8.0) were similar in patients in the early-start T&E and fixed 2q8 regimen treatment arms, respectively. The proportion maintaining visual acuity at Week 52 was 98.5% and 97.8% in early-start T&E and fixed 2q8 regimens, respectively, similar or better than observed in pivotal trials. By Week 52, mean central retinal thickness was decreased by 160 and 178 µm on average from baseline in early-start T&E and fixed 2q8 regimens, respectively. The proportion with study eye ocular serious adverse events was 0.0% (early-start T&E) and 2.2% (fixed 2q8 regimen). This safety profile is consistent with previous studies.

Conclusions : Interim 52-week results from ARIES support outcomes with a T&E IAI regimen after the first 8-week interval and are consistent with a 2q8 fixed treatment approach over the first year in treating nAMD. The observed average reduction in injection number after loading is clinically relevant.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.