EFFICACY AND SAFETY OF INTRAVITREAL AFLIBERCEPT USING A TREAT-AND-EXTEND REGIMEN FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: The ARIES Study: A Randomized Clinical Trial

Abstract

Background/purpose: Treating neovascular age-related macular degeneration with intravitreal aflibercept treat-and-extend (T&E) can reduce treatment burden. ARIES assessed whether intravitreal aflibercept early-start T&E was noninferior to late-start T&E.

Methods: A randomized, open-label, Phase 3b/4 study that included treatment-naïve patients aged ≥50 years with the best-corrected visual acuity 73-25 Early Treatment Diabetic Retinopathy Study letters and active choroidal neovascularization secondary to AMD. Patients received 2 mg intravitreal aflibercept at Week (W) 0, W4, W8, and W16. At W16, patients were randomized 1:1 to early-start (2W interval adjustments) or late-start T&E (8W intervals until W48 then 2W interval adjustments). Primary endpoint: the best-corrected visual acuity change from randomization to W104.

Results: Two-hundred seventy-one patients were randomized. The mean (SD) best-corrected visual acuity at baseline was 60.2 (12.1; early-T&E) and 61.3 (10.8; late-T&E) letters. The mean (SD) best-corrected visual acuity change (W16-104) was -2.1 (11.4) versus -0.4 (8.4) letters (early-T&E vs. late-T&E; least-squares mean difference: -2.0; 95% confidence interval: -4.75 to 0.71; P = 0.0162 for noninferior); +4.3 (13.4) versus +7.9 (11.9) letters (W0-104). The mean (SD) number of injections was 12.0 (2.3) versus 13.0 (1.8). From baseline to W104, 93.4% and 96.2% maintained best-corrected visual acuity; the mean (SD) central retinal thickness change was -161.6 (135.6) µm and -158.6 (125.1) µm. The last injection interval (W104) was ≥12W for 47.2% and 51.9% of patients.

Conclusion: Outcomes were similar between patients with neovascular age-related macular degeneration treated with an intravitreal aflibercept early-T&E or late-T&E regimen after initial dosing, with one injection difference over 2 years.

Trial registration: ClinicalTrials.gov Identifier: NCT02581891 https://ichgcp.net/clinical-trials-registry/NCT02581891. Supplemental Digital Contents (files 1 http://links.lww.com/IAE/B419).

Conflict of interest statement

P. Mitchell has received consulting fees from Bayer, Novartis, and Allergan and is an ARIES Steering Committee member. F. Holz has served as a consultant for Acucela, Apellis Pharmaceuticals, Bayer, Boehringer-Ingelheim, Bioeq/Formycon AG, Roche/Genentech, Geuder AG, Graybug Vision, Heidelberg Engineering, Chengdu Kanghong Pharmaceuticals, Lin Bioscience, Novartis, Pixium Vision, Oxurion, and Stealth BioTherapeutics; has received research support from Acucela, Apellis Pharmaceuticals, Bayer, Bioeq/Formycon AG, CenterVue, Roche/Genentech, Heidelberg Engineering, Chengdu Kanghong Pharmaceuticals, NightstaRx, Novartis, Optos, Pixium Vision, and Zeiss Pharma; has received honoraria or travel reimbursement from Acucela, Apellis Pharmaceuticals, Bayer, Ellex, Roche/Genentech, Graybug Vision, Heidelberg Engineering, Lin Bioscience, Novartis, Pixium Vision, Oxurion, Stealth BioTherapeutics, and Zeiss Pharma; and is an ARIES Steering Committee member. P. Hykin has received consultant fees from Bayer HealthCare, Novartis, and Allergan; has received travel support to participate in review activities for meetings from Bayer; has received support for provision of writing assistance, medicines, equipment, or administrative support from Bayer; has received payment for lectures and support for conference attendance from Allergan and Novartis; and is an ARIES Steering Committee member. S. Wolf has served as a consultant for Allergan, Bayer, Boehringer-Ingelheim, Chengdu Kanghong Biotech, Heidelberg Engineering, Novartis, Oxurion, Zeiss, and Roche; has received grant support from Heidelberg Engineering; and is an ARIES Steering Committee member. H. Allmeier, G. Lambrou, and T. Schmelter are employees of Bayer. T. Schmelter owns stocks of Bayer AG. E. Souied is an ARIES Steering Committee member. E. Midena is an ARIES Steering Committee member.

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.

Figures

Fig. 1.

ARIES study design. *Patients were stratified based on visual outcomes from baseline to Week 16 (

Fig. 2.

Patient disposition. *One patient discontinued during the follow-up period after completion of treatment.

Fig. 3.

A. The mean BCVA change (Week 16 to Week 104). B. Absolute BCVA (baseline to Week 104; PPS). Error bars indicate standard error of the mean. Analyses were conducted as a last observation carried forward from the PPS. *Adjusted treatment difference (least squares means). †CI excludes −5 (prespecified noninferiority margin).

Fig. 4.

Duration of last treatment interval up to Week 104 (PPS). Analyses were conducted as a LOCF from the PPS. Intervals greater than 16 weeks were considered minor deviations and were included in the PPS. LOCF, last observation carried forward.