Comparative Efficacy of Brolucizumab in the Treatment of Neovascular Age-Related Macular Degeneration: A Systematic Literature Review and Network Meta-Analysis

Adv Ther. 2022 Aug;39(8):3425-3448. doi: 10.1007/s12325-022-02193-3. Epub 2022 Jun 9.

Abstract

Introduction: A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy of brolucizumab relative to other anti-vascular endothelial growth factor (VEGF) treatments for neovascular age-related macular degeneration (nAMD) at 1 and 2 years, and overall safety and injection frequency of each treatment.

Methods: An SLR identifying randomized controlled trials (RCTs) published before June 2021 according to a pre-specified protocol was followed by a Bayesian NMA to compare brolucizumab (6 mg q12w/q8w) against sham and all relevant anti-VEGF regimens. Pooled mean injection frequency, serious adverse ocular events, and discontinuation rates were estimated for each treatment regimen.

Results: Nineteen RCTs were included in NMA base-case analysis. Brolucizumab (6 mg q12w/q8w) with loading-phase (LP) demonstrated superior best-corrected visual acuity (BCVA) gains to sham both at year 1 (mean difference 16.8 [95%CrI 13.3, 20.4]) and year 2 (mean difference 21.2 [95%CrI 17.4, 25.0]) and was comparable to other anti-VEGFs. Brolucizumab (6 mg q12w/q8w) also showed superior retinal thickness reduction to most comparators including ranibizumab (0.5 mg q4w; year 1 mean difference - 50.1 [95%CrI - 70.3, - 29.8]; year 2 mean difference - 49.5 [95%CrI - 70.8, - 28.6]), aflibercept (2 mg q8w; year 1 mean difference - 39.7 [95%CrI - 52.9, - 26.4]; year 2 mean difference - 35.0 [95%CrI - 49.1, - 21.4]), and faricimab (6 mg q16w/q8w; year 1 mean difference - 27.6 [95%CrI - 42.3, - 12.8]). Brolucizumab (6 mg q12w/q8w) showed similar rates of treatment discontinuation and serious and overall adverse events (both years). At year 2, pooled annualized injection frequency was lowest for brolucizumab (6 mg q12w/q8w) and highest for ranibizumab (0.5 mg q4w) at 5.7 and 11.5 injections annually, respectively.

Conclusion: Among all licensed anti-VEGF treatments, brolucizumab showed superior reduction in retinal thickness and comparable BCVA gains and discontinuation rates, despite having the lowest injection frequency. The current study provides the most up-to-date, robust comparison of treatments for nAMD.

Keywords: Anti-VEGF; Brolucizumab; NMA; Neovascular age-related macular degeneration; Network meta-analysis; nAMD.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Review
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / adverse effects
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Child, Preschool
  • Humans
  • Infant
  • Intravitreal Injections
  • Macular Degeneration* / drug therapy
  • Network Meta-Analysis
  • Ranibizumab* / therapeutic use
  • Receptors, Vascular Endothelial Growth Factor / therapeutic use
  • Recombinant Fusion Proteins / adverse effects
  • Vascular Endothelial Growth Factor A / therapeutic use
  • Visual Acuity

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Recombinant Fusion Proteins
  • Vascular Endothelial Growth Factor A
  • Receptors, Vascular Endothelial Growth Factor
  • brolucizumab
  • Ranibizumab