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

Introduction: 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.

Methods: 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 6 mg (every 12 [Q12W]/every 8 weeks [Q8W]) with relevant aflibercept 2 mg and ranibizumab 0.5 mg regimens.

Results: Fourteen studies were included in the NMA. At 1-year follow-up, the various aflibercept 2 mg and ranibizumab 0.5 mg regimens were mostly comparable with brolucizumab 6 mg Q12W/Q8W across key visual and anatomical outcomes, except brolucizumab 6 mg was favoured over ranibizumab 0.5 mg every 4 weeks (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 0.5 mg pro re nata for CFB in diabetic retinopathy severity scale, and retinal thickness. At year 2, where data were available, brolucizumab 6 mg 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.

Conclusion: Brolucizumab 6 mg Q12W/Q8W was comparable or superior to aflibercept 2 mg and ranibizumab 0.5 mg regimens for various visual and anatomical efficacy outcomes and discontinuation rates.

Keywords: Aflibercept; Anti-VEGF; Best-corrected visual acuity; Brolucizumab; Diabetic macular oedema; Diabetic retinopathy; Network meta-analysis; Ranibizumab; Retinal thickness; Visual impairment.