Garweg, JustusJustusGarwegŠtefanickova, JanaJanaŠtefanickovaHoyng, CarelCarelHoyngNiesen, TobiasTobiasNiesenSchmelter, ThomasThomasSchmelterLeal, SergioSergioLealSivaprasad, SobhaSobhaSivaprasad2024-10-092024-10-092022-06https://boris-portal.unibe.ch/handle/20.500.12422/70165INTRODUCTION The purpose was to compare two flexible regimens of intravitreal aflibercept (IVT-AFL) with fixed dosing every 8 weeks, beyond the first year of treatment, in patients with diabetic macular edema (DME). VIOLET was a 100-week, randomized, Phase IIIb, non-inferiority study in patients with center-involving DME previously treated with IVT-AFL for ≥ 1 year according to the European label. METHODS Patients received an initial dose of IVT-AFL at study baseline and were randomly assigned (1:1:1) to treat-and-extend (T&E), pro re nata (PRN), or fixed regimens. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline (randomization) to Week 52. RESULTS Full analysis set comprised 458 patients (baseline mean BCVA: 72.5, 71.0, and 72.7 letters in the T&E, PRN, and fixed-dose groups, respectively). Patients received a mean (min-max) of 10.0 (2-14; T&E), 11.5 (1-25; PRN), and 12.3 (3-13; fixed) injections over 100 weeks, with 13.3 (4-23), 25.0 (3-29), and 16.1 (5-25) clinic visits, respectively. At Week 52, mean (± standard deviation) BCVA changes from baseline were + 0.5 ± 6.7 (T&E), + 1.7 ± 6.8 (PRN), and + 0.4 ± 6.7 (fixed-dosing) letters (least squares mean difference [95% confidence interval]: T&E 0.01 [- 1.46, 1.47] and PRN 0.95 (- 0.52, 2.42) letters versus fixed dosing; p < 0.0001 for both non-inferiority tests [4-letter margin]). The IVT-AFL safety profile was consistent with previous studies. CONCLUSION The treatment burden associated with intravitreal injections for DME is lowest with T&E regimens, but there are a range of flexible IVT-AFL dosing regimens, allowing physicians to adopt an individualized treatment plan. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT02818998.enAflibercept Diabetic retinopathy Intravitreal injections Macular edema Treatment outcome Vascular endothelial growth factor600 - Technology::610 - Medicine & healtharticle10.48350/1692723541222710.1007/s12325-022-02119-z