Comparison of treat-and-extend (T&E) dosing regimens and visual outcomes in the ARIES and ALTAIR studies of intravitreal aflibercept (IVT-AFL) in neovascular age-related macular degeneration (nAMD)

Abstract

Purpose : To compare the criteria used for adjusting T&E treatment intervals and visual outcomes in two large multicenter, randomized Phase 4 studies (ARIES and ALTAIR) evaluating the efficacy and safety of IVT-AFL in nAMD using T&E dosing regimens.

Methods : In ARIES (NCT02581891; 104 weeks) and ALTAIR (NCT02305238; 96 weeks), patients received 3 initial monthly doses of 2mg IVT-AFL (Weeks [W] 0, 4, and 8), followed by an injection at W16. In ARIES, patients were randomized at W16 to an early-start T&E arm (T&E extended in 2-week steps) or a late-start T&E arm (2mg IVT-AFL every 8 weeks until W52, followed by T&E in 2-week steps). In ALTAIR, patients were randomized at W16 to T&E groups with either a 2 or 4-week injection interval adjustment. The T&E treatment interval adjustment criteria differed between the studies. ARIES criteria for interval adjustment were: no intraretinal fluid AND no new neovascularization or hemorrhage AND subretinal thickness <50μm. ALTAIR criteria for interval extension were: no fluid AND ≤5 Early Treatment Diabetic Retinopathy Study (ETDRS) letter loss AND central retinal thickness increase ≤100µm AND no new neovascularization or hemorrhage. Additionally, ALTAIR introduced criteria to allow maintenance of treatment intervals.

Results : Combined average outcomes of the two treatment arms in each study (early/late-start in ARIES and 2 vs 4-week intervals in ALTAIR) were similar: in ARIES/ALTAIR mean best-corrected visual acuity (ETDRS letters) was 60.7/55.0 at baseline; 68.1/64.0 at randomization (W16); 69.7/63.7 at Year 1 (W52); and 66.8/61.9 at Year 2 (W104/W96), respectively. A mean last injection interval of ≥12 and ≥16 weeks was achieved in 49.5%/58.5% and 28.6%/43.9% of patients in ARIES/ALTAIR, respectively. The mean number of injections in ARIES/ALTAIR at W52, respectively, was 7.5/7.0 and at study end was 12.5 (ARIES, W104) and 10.4 (ALTAIR, W96).

Conclusions : ARIES and ALTAIR demonstrated that treatment intervals of ≥12 weeks and good improvement of visual outcomes (>5-letter gain) can be achieved with IVT-AFL T&E dosing in patients with nAMD. Fine-tuning of the T&E regimen by means of an interval-maintenance step and of functional criteria, as introduced by ALTAIR, could potentially further reduce patient burden by increasing treatment intervals.

This is a 2020 ARVO Annual Meeting abstract.