Efficacy and Safety of Intravitreal Aflibercept Treat-and-Extend Regimens in Exudative Age-Related Macular Degeneration: 52- and 96-Week Findings from ALTAIR

Abstract

Purpose: To evaluate efficacy and safety of intravitreal injections of aflibercept (IVT-AFL) treat-and-extend (T&E) dosing regimens in treatment-naïve patients with exudative agerelated macular degeneration (AMD).Methods: Adults aged at least 50 years old with exudative AMD and best-corrected visual acuity (BCVA) of 73-25 Early Treatment Diabetic Retinopathy Study (ETDRS) letters were included. Patients received three monthly doses of IVT-AFL 2 mg. At week 16, patients were randomized 1:1 to IVT-AFL T&E with either 2-or 4-week adjustments. The primary endpoint was mean change in BCVA from baseline to week 52. Outcomes were assessed at weeks 52 and 96. Results: Baseline characteristics were comparable between the groups (n = 123 each). Over 52 weeks, mean number of injections was 7.2 and 6.9 and mean last injection interval was 10.7 and 11.8 weeks, for the 2-and 4-week groups, respectively. From baseline, mean change in BCVA was ? 9.0 and ? 8.4 letters (week 52) and ? 7.6 and ? 6.1 letters (week 96); mean change in central retinal thickness was -134.4 lm and -126.1 lm (week 52) and -130.5 lm and -125.3 lm (week 96). Last injection interval before week 52 was at least 12 weeks in 42.3% and 49.6% of patients and 56.9% and 60.2% before week 96. Over 96 weeks, mean number of injections was 10.4 (both groups). The safety profile of IVT-AFL was consistent with previous reports. Conclusions: IVT-AFL administered using two different T&E regimens for treatment-naïve exudative AMD improved functional and anatomic outcomes at week 52 and outcomes were Enhanced Digital Features To view enhanced digital features for this article go to https://doi.org/10.6084/ m9.figshare.11603511.maintained to week 96. Outcomes were similar between the 2-and 4-week groups. Trial Registration: ClinicalTrials.gov identifier, NCT02305238. Key Summary PointsWhy carry out this study?The goal of proactive flexible treat-andextend (T&E) regimens is to reduce the treatment burden associated with antivascular endothelial growth factor (VEGF) therapy, while maintaining a patient's visual acuity gains.The aim of this study was to evaluate the efficacy and safety of intravitreal aflibercept (IVT-AFL) T&E dosing regimens in treatment-naïve patients with exudative age-related macular degeneration (AMD).What was learned from the study?IVT-AFL administered using either 2-or 4-week adjustment T&E regimens in treatment-naïve patients with exudative AMD improved functional (best-corrected visual acuity ? 9.0 and ? 8.4 letters) and anatomic outcomes (central retinal thickness -134.4 and -126.1 lm) at 52 weeks; functional and anatomic outcomes were maintained over 96 weeks.A large proportion of patients (35.1% and 40.5%) had an intended injection interval of 16 weeks at week 52.The incidence of treatment-emergent adverse events was consistent with the known safety profile of IVT-AFL.IVT-AFL T&E regimens were efficacious and safe over 96 weeks of treatment using either 2-or 4-week adjustments.

One-Year Results of a Treat-and-Extend Regimen of Intravitreal Aflibercept for Polypoidal Choroidal Vasculopathy

“…In contrast, TAE uses a shortened injection interval when exudative changes remain or worsen and an extended injection interval when exudative changes disappear [14][15][16][17][18][19]. In the current study, the administration interval was extended by 2 weeks when the exudative changes disappeared after at least three monthly loading treatments, with administrations reset to the initial 1-month interval after any recurrence.…”

<p>Therapeutic Potential of the Ranibizumab Port Delivery System in the Treatment of AMD: Evidence to Date</p>

“…Of note, the randomized Phase 4 ALTAIR trial demonstrated a last intravitreal aflibercept injection interval of at least 12 weeks with a 2 or 4 week treat-and-extend (TREX) strategy in 57% and 60% of treatment-naive patients with nAMD by week 96. 29 The randomized Phase 3 trials of HAWK and HARRIER demonstrated that approximately 50% of patients with untreated, active nAMD can be maintained on 12 week interval treatments of intravitreal brolucizumab without rescue therapy. 30 From clinical practice and published data, the q12 week injection intervals for aflibercept and brolucizumab are the longest demonstrated efficacious duration of the currently available medications.…”

The Tie2 signaling pathway in retinal vascular diseases: a novel therapeutic target in the eye

“…Yet, there remain unmet needs for the treatment of these conditions. The current pharmacologic agents are indicated for repeated intravitreal (IVT) injections every 1-3 months [6][7][8], although less often retreatment has shown to be effective [10][11][12][13][14][15]. This significant treatment burden is unsustainable, and many patients receive fewer than the recommended number of injections with commensurately suboptimal visual outcomes [16][17][18][19][20][21].…”