Patients with Neovascular Age-Related Macular Degeneration Requiring Intensive Intravitreal Aflibercept Treatment: An ARIES Post Hoc Analysis

Abstract

Introduction: The aim of this post hoc analysis of the ARIES study is to explore the requirement for intravitreal aflibercept (IVT-AFL) treatment intervals of < 8 weeks (w) in patients with neovascular age-related macular degeneration (nAMD), and to assess vision and anatomic outcomes in such patients who require more intensive treatment.

Methods: ARIES was a multicenter, randomized, phase 3b/4 study that investigated the efficacy of two IVT-AFL proactive, individualized, treat-and-extend regimens over 2 years in treatment-naïve patients with nAMD. Patients were determined as injection-intensive if the study investigator identified that a treatment interval of < 8 w was needed and if they had ≥ 1 interval of < 8 w after three initial monthly doses. Treatment intervals could be extended subsequently if extension criteria were met. This is a post hoc analysis of patients enrolled in ARIES and statistical analysis is descriptive.

Results: Of 269 patients in the combined treatment arms, 23.0% (n = 62) were injection-intensive (Year 1: 13.8% [n = 37]; Year 2: 9.3% [n = 25]). Time from IVT-AFL initiation to injection-intensive determination varied (range, 16-100 w; median: 43.2 w). Mean treatment interval was 8.4 w before and 6.1 w after injection-intensive determination. Overall, 59.7% achieved treatment intervals of ≥ 8 w following injection-intensive determination. Vision improvements from baseline to Week 104 were smaller for injection-intensive patients than non-injection-intensive patients (mean [SD] best-corrected visual acuity change: + 2.3 [15.6] vs. + 5.9 [12.3] letters). Anatomic outcomes were similar between injection-intensive and non-injection-intensive patients (central retinal thickness change from baseline to Week 104: - 160 [154] vs. - 167 [136] µm).

Conclusions: In ARIES, 23% of treatment-naïve patients with nAMD experienced at least one treatment interval of < 8 w. Injection-intensive patients showed improved vision and anatomic outcomes. For most, treatment intervals could be extended to ≥ 8 w following injection-intensive determination.

Clinicaltrials: gov Identifier: NCT02581891.

Keywords: Injection-intensive; Intravitreal aflibercept; Neovascular age-related macular degeneration; Treat-and-extend; Treatment intervals; Treatment outcomes.

© 2022. The Author(s).

Figures

Fig. 1

Kaplan–Meier plot for time to injection-intensive visit (all injection-intensive patients)

Fig. 2

Duration of the longest interval after the injection-intensive visit. Categorization: 8 weeks = 49–63 days; 10 weeks = 64–77 days; 12 weeks = 78–91 days; 14 weeks = 92–105 days; 16 weeks = 106–119 days; ≥ 16 weeks =  ≥ 119 days. Max maximum, Min minimum, SD standard deviation

Fig. 3

a BCVA and b CRT outcomes by injection-intensive status. Full analysis set. Last observation carried forward. Injection-intensive visit could occur at any time from randomization (Week 16) to Week 104. BCVA best-corrected visual acuity, BL baseline, CRT central retinal thickness, SEM standard error of the mean