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

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.

• Authors: Robert P Finger, Natalie Dennis, Rita Freitas, Arthur Quenéchdu, Andreas Clemens, Helene Karcher, Eric H Souied
• Journal: Advances in therapy (Adv Ther) Vol. 39 Issue 8 Pg. 3425-3448 (08 2022) ISSN: 1865-8652 [Electronic] United States
• PMID: 35678996 (Publication Type: Comparative Study, Journal Article, Meta-Analysis, Review, Systematic Review, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

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

Topics

• 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