Intravitreal Aflibercept for Neovascular Age-Related Macular Degeneration Beyond One Year of Treatment: AZURE, a Randomized Trial of Treat-and-Extend vs. Fixed Dosing.

Abstract

INTRODUCTION:

AZURE was a 76-week, randomized, open-label, parallel-group, phase IIIb noninferiority study comparing the efficacy and safety of intravitreal aflibercept (IVT-AFL) in a treat-and-extend (T&E) regimen with fixed dosing in patients with neovascular age-related macular degeneration (nAMD) previously receiving IVT-AFL for ≥ 1 year.

METHODS:

Patients were aged ≥ 51 years and had completed ≥ 1 year of IVT-AFL treatment prior to enrollment (IVT-AFL once per month [- 1 or + 2 weeks] for 3 months followed by IVT-AFL every 2 months [6-12 weeks]). Patients were randomly assigned (1:1) to receive IVT-AFL 2 mg in either a T&E (minimum treatment interval of 8 weeks with no upper limit, adjusted according to functional and anatomic outcomes, as assessed by the investigator; n = 168), or a fixed dosing regimen (treatment every 8 weeks [± 3 days]; n = 168). The primary endpoint was best-corrected visual acuity (BCVA) change from baseline to week (W) 52. The key secondary endpoint was the proportion of patients maintaining vision (< 15-letter loss) at W52.

RESULTS:

The full analysis set comprised 332 patients (T&E: n = 165; fixed dosing: n = 167). Mean BCVA change (baseline to W52) was - 0.3 ± 7.5 vs. - 0.5 ± 8.4 letters (T&E vs. fixed dosing; least-squares mean difference [95% CI]: 0.22 [- 1.51 to 1.96] letters; P < 0.0001 for noninferiority test [5-letter margin]). From baseline to W52, 95.2% (T&E) and 94.0% (fixed dosing) of patients maintained vision. Mean central subfield thickness change from baseline to W52 was - 24 ± 55 (T&E) and - 33 ± 47 (fixed dosing) µm. Last treatment interval to W76 was ≥ 12 weeks for 37.0% of T&E patients. No new safety signals were identified.

CONCLUSION:

IVT-AFL T&E can achieve similar functional and anatomic outcomes to fixed dosing every 8 weeks over 52 weeks in patients with nAMD who have completed ≥ 1 year of treatment, while reducing treatment burden.

TRIAL REGISTRATION:

ClinicalTrials.gov Identifier: NCT02540954.

• Authors: Laurent Kodjikian, Lluís Arias Barquet, András Papp, Peter J Kertes, Edoardo Midena, Jan Ernest, Rufino Silva, Thomas Schmelter, Tobias Niesen, Sergio Leal
• Journal: Advances in therapy (Adv Ther) Vol. 41 Issue 3 Pg. 1010-1024 (Mar 2024) ISSN: 1865-8652 [Electronic] United States
• PMID: 38183525 (Publication Type: Clinical Trial, Phase III, Equivalence Trial, Journal Article, Randomized Controlled Trial)
• Copyright: © 2024. The Author(s).

Chemical References

• aflibercept
• Receptors, Vascular Endothelial Growth Factor
• Recombinant Fusion Proteins

Topics

• Humans
• Middle Aged
• Intravitreal Injections
• Macular Degeneration (drug therapy)
• Receptors, Vascular Endothelial Growth Factor (therapeutic use)
• Recombinant Fusion Proteins (therapeutic use)
• Treatment Outcome
• Visual Acuity
• Aged