Hypothetical Switch of Anti-Vascular Endothelial Growth Factor in Neovascular Age-Related Macular Degeneration: An ARIES Post Hoc Analysis

Abstract

Introduction: Switching to an alternative anti-vascular endothelial growth factor (anti-VEGF) agent has been suggested for patients with neovascular age-related macular degeneration (nAMD) who have a suboptimal response to initial therapy. However, post hoc analyses of some studies have shown that continuation of initial anti-VEGF therapy is, in many cases, associated with stable visual outcomes or gradual gains.

Methods: This ARIES (ClinicalTrials.gov Identifier: NCT02581891) post hoc analysis describes outcomes in patients with treatment-naïve nAMD receiving treat-and-extend intravitreal aflibercept (IVT-AFL) for 104 weeks, who were identified as meeting criteria for an early hypothetical switch. Patients were categorized retrospectively according to six criteria (presence of central intraretinal and/or subretinal fluid at week 8 or 24, with/without a next planned treatment interval ≤ 8 weeks, and with/without gains in best-corrected visual acuity [BCVA] ≤ 5 letters [with absolute BCVA < 70 letters]).

Results: Hypothetical switch criteria were largely met due to the presence of central subretinal fluid rather than intraretinal fluid. Depending on the criterion, 8-46% of patients were considered to be hypothetical switchers. BCVA outcomes were not worse in the hypothetical switchers, irrespective of criteria. Using criteria of intraretinal/subretinal fluid at week 24 and a next planned treatment interval ≤ 8 weeks, mean changes in BCVA (letters) from baseline in hypothetical switchers and non-switchers were: + 6.1 (95% confidence interval [CI] 3.4, 8.8) and + 6.6 (95% CI 4.7, 8.6), respectively, at week 24; + 8.2 (95% CI 5.0, 11.3) and + 7.5 (95% CI 5.3, 9.7), respectively, at week 52; and + 5.7 (95% CI 1.3, 10.1) and + 3.4 (95% CI 0.1, 6.7), respectively, at week 104.

Conclusions: In newly diagnosed nAMD, there appears little rationale for early switching from IVT-AFL since, with continuous proactive treatment, comparable visual gains can be achieved by patients meeting hypothetical switch criteria compared with those who initially respond well on a treat-and-extend regimen. However, further prospective studies are needed.

Trial registration: ClinicalTrials.gov Identifier: NCT02581891. Video summary of the ARIES Post Hoc Analysis "Hypothetical Switch of Anti-Vascular Endothelial Growth Factor in Neovascular Age-Related Macular Degeneration" (MP4 54283 KB).

Keywords: Aflibercept; Age-related macular degeneration; Intravitreal injections; Optical coherence tomography; Treat-and-extend; Treatment outcome; Vascular endothelial growth factors.

© 2022. The Author(s).

Figures

Fig. 1

Proportion of patients in the per-protocol set with central IRF and central SRF over time, grouped post baseline by hypothetical switch criteria 1, 3, and 5: the presence of central fluid at week 8 (a), week 24 (b), week 24 (c) and next planned treatment interval ≤ 8 weeks. The dashed box indicates the “index” weeks at which time point hypothetical switch criteria were defined. IRF Intraretinal fluid, SRF subretinal fluid

Fig. 2

Mean (± standard error of the mean [SEM]) absolute BCVA values over time in patients in the per-protocol population grouped post-baseline by hypothetical switch criteria 1, 3, and 5: the presence of central fluid at week 8 (a), week 24 (b), and week 24 (c) and next planned treatment interval ≤ 8 weeks. The dashed line indicates the “index” weeks at which point hypothetical switch criteria were defined. BCVA Best-corrected visual acuity, BL baseline, CI confidence interval

Fig. 3

Mean (± SEM) absolute CRT values over time in patients in the per-protocol population grouped post baseline by hypothetical switch criteria 1, 3, and 5: the presence of central fluid at week 8 (a), week 24 (b), and week 24 (c) and next planned treatment interval ≤ 8 weeks. The dashed line indicates the “index” weeks at which point hypothetical switch criteria were defined. CRT Central retinal thickness