Efficacy and Safety of Brolucizumab, Aflibercept, and Ranibizumab for the Treatment of Patients with Visual Impairment Due to Diabetic Macular Oedema: A Systematic Review and Network Meta-Analysis.

Abstract

Key clinical guidelines recommend anti-vascular endothelial growth factor (VEGF) therapy as first-line treatment for visual impairment due to diabetic macular oedema (DMO). A systematic literature review (SLR) and network meta-analysis (NMA) were conducted comparing the relative efficacy of the anti-VEGF brolucizumab with a focused network of the most relevant comparator dosing regimens approved in countries other than the USA (aflibercept, ranibizumab). The safety and tolerability of brolucizumab were also assessed. A broad SLR was conducted to identify randomised controlled trials to ensure all relevant potential comparators were captured. Identified studies were refined to those appropriate for inclusion in the NMA. A Bayesian NMA was conducted comparing brolucizumab 6mg (every 12 [Q12W]/every 8weeks [Q8W]) with relevant aflibercept 2mg and ranibizumab 0.5mg regimens. Fourteen studies were included in the NMA. At 1-year follow-up, the various aflibercept 2mg and ranibizumab 0.5mg regimens were mostly comparable with brolucizumab 6mg Q12W/Q8W across key visual and anatomical outcomes, except brolucizumab 6mg was favoured over ranibizumab 0.5mg every 4weeks (Q4W) for the change from baseline (CFB) in best-corrected visual acuity (BCVA), and BCVA loss/gain of pre-specified numbers of letters, and over ranibizumab 0.5mg pro re nata for CFB in diabetic retinopathy severity scale, and retinal thickness. At year2, where data were available, brolucizumab 6mg showed similar results across efficacy outcomes versus all other anti-VEGFs. In most cases, discontinuation rates (all cause, and due to adverse events [AE]) and serious and overall rates of AEs excluding ocular inflammatory events were similar (in unpooled and pooled-treatment analyses) versus comparators. Brolucizumab 6mg Q12W/Q8W was comparable or superior to aflibercept 2mg and ranibizumab 0.5mg regimens for various visual and anatomical efficacy outcomes and discontinuation rates.