Brown, David MDavid MBrownEmanuelli, AndrésAndrésEmanuelliBandello, FrancescoFrancescoBandelloBarranco, Jose Juan EscobarJose Juan EscobarBarrancoFigueira, JoãoJoãoFigueiraSouied, EricEricSouiedWolf, SebastianSebastianWolf0000-0002-7467-7028Gupta, VishaliVishaliGuptaNgah, Nor FarizaNor FarizaNgahLiew, GeraldGeraldLiewTuli, RamanRamanTuliTadayoni, RaminRaminTadayoniDhoot, DilsherDilsherDhootWang, LixinLixinWangBouillaud, EmmanuelEmmanuelBouillaudWang, YingYingWangKovacic, LidijaLidijaKovacicGuerard, NicolasNicolasGuerardGarweg, JustusJustusGarweg2024-10-252024-10-252022-06https://boris-portal.unibe.ch/handle/20.500.12422/166282PURPOSE To compare the efficacy and safety of brolucizumab with aflibercept in patients with diabetic macular edema (DME). DESIGN Double-masked, 100-week, multicenter, active-controlled, randomized trials. METHODS Subjects were randomized 1:1:1 to brolucizumab 3 mg/6 mg or aflibercept 2 mg in KESTREL (n = 566) or 1:1 to brolucizumab 6 mg or aflibercept 2 mg in KITE (n = 360). Brolucizumab groups received 5 loading doses every 6 weeks (q6w) followed by 12-week (q12w) dosing, with optional adjustment to every 8 weeks (q8w) if disease activity was identified at predefined assessment visits; aflibercept groups received 5 doses every 4 weeks (q4w) followed by fixed q8w dosing. The primary endpoint was best-corrected visual acuity (BCVA) change from baseline at Week 52; secondary endpoints included the proportion of subjects maintained on q12w dosing, change in Diabetic Retinopathy Severity Scale score, and anatomical and safety outcomes. RESULTS At Week 52, brolucizumab 6 mg was noninferior (NI margin 4 letters) to aflibercept in mean change in BCVA from baseline (KESTREL: +9.2 letters vs +10.5 letters; KITE: +10.6 letters vs +9.4 letters; P < .001), more subjects achieved central subfield thickness (CSFT) <280 µm, and fewer had persisting subretinal and/or intraretinal fluid vs aflibercept, with more than half of brolucizumab 6 mg subjects maintained on q12w dosing after loading. In KITE, brolucizumab 6 mg showed superior improvements in change of CSFT from baseline over Week 40 to Week 52 vs aflibercept (P = .001). The incidence of ocular serious adverse events was 3.7% (brolucizumab 3 mg), 1.1% (brolucizumab 6 mg), and 2.1% (aflibercept) in KESTREL; and 2.2% (brolucizumab 6 mg) and 1.7% (aflibercept) in KITE. CONCLUSION Brolucizumab 6 mg showed robust visual gains and anatomical improvements with an overall favorable benefit/risk profile in patients with DME.en600 - Technology::610 - Medicine & healtharticle10.48350/1814933503841510.1016/j.ajo.2022.01.004