Abstract
Background: We aimed to evaluate the comparative efficacy and safety of anti–vascular endothelial growth factor (anti-VEGF) monotherapy to identify its utilization and prioritization in patients with neovascular age-related macular degeneration (nAMD). Methods: Eligible studies included randomized controlled trials comparing the recommended anti-VEGF agents (ranibizumab, bevacizumab, aflibercept, brolucizumab, and conbercept) under various therapeutic regimens. Outcomes of interest included the mean change in best-corrected visual acuity (BCVA), serious adverse events, the proportion of patients who gained ≥15 letters or lost <15 letters in BCVA, the mean change in central retinal thickness, and the number of injections within 12 months. Results: Twenty-seven trials including 10,484 participants and eighteen treatments were identified in the network meta-analysis. The aflibercept 2 mg bimonthly, ranibizumab 0.5 mg T&E, and brolucizumab 6 mg q12w/q8w regimens had better visual efficacy. Brolucizumab had absolute superiority in anatomical outcomes and a relative advantage of safety, as well as good performance of aflibercept 2 mg T&E. The proactive regimens had slightly better efficacy but a slightly increased number of injections versus the reactive regimen. Bevacizumab had a statistically non-significant trend toward a lower degree of efficacy and safety. Conclusion: The visual efficacy of four individual anti-VEGF drugs is comparable. Several statistically significant differences were observed considering special anti-VEGF regimens, suggesting that brolucizumab 6 mg q12w/q8w, aflibercept 2 mg bimonthly or T&E, and ranibizumab 0.5 mg T&E are the ideal anti-VEGF regimens for nAMD patients. In the current landscape, based on the premise of equivalent efficacy and safety, the optimal choice of anti-VEGF monotherapies seems mandatory to obtain maximal benefit.
Highlights
Age-related macular degeneration (AMD) is a progressive and degenerative retinal disease that causes severe and irreversible vision loss in people older than 50 years (Flaxel et al, 2020)
Choroidal neovascularization (CNV) is the typical pathological feature of neovascular AMD, which is controlled by various growth factors, such as vascular endothelial growth factor (VEGF), and typified by an anomalous angiogenic process (Bressler, 2009)
We report comprehensive monotherapy-based mixed treatment comparisons (Bayesian network meta-analysis) of efficacy, safety, and therapeutic frequency in patients receiving anti-VEGF monotherapy, which can overcome the shortage of direct comparison trials and combine direct and indirect data to compare two or more interventions simultaneously to identify the utilization and prioritization of anti-VEGF monotherapies in neovascular AMD (nAMD) patients
Summary
Age-related macular degeneration (AMD) is a progressive and degenerative retinal disease that causes severe and irreversible vision loss in people older than 50 years (Flaxel et al, 2020). Numerous studies have confirmed the efficacy and safety of anti-VEGF therapy, and published guidelines currently recommend antiVEGF therapy as the first-line treatment for patients with nAMD (23 January 2018; Flaxel et al, 2020; Yeung et al, 2021), including ranibizumab (Lucentis, Genentech Inc.), bevacizumab (Avastin, Genentech Inc.), aflibercept (Eylea, Regeneron Pharmaceuticals, Inc.), conbercept (Lumitin; Chengdu Kanghong, Inc.) and, recently, brolucizumab (Beovu, Novartis, Inc.) (Schmidt-Erfurth et al, 2014; Flaxel et al, 2020). We report comprehensive monotherapy-based mixed treatment comparisons (Bayesian network meta-analysis) of efficacy (visual acuity and anatomical structure), safety, and therapeutic frequency in patients receiving anti-VEGF monotherapy, which can overcome the shortage of direct comparison trials and combine direct and indirect data to compare two or more interventions simultaneously to identify the utilization and prioritization of anti-VEGF monotherapies in nAMD patients. We aimed to evaluate the comparative efficacy and safety of anti–vascular endothelial growth factor (anti-VEGF) monotherapy to identify its utilization and prioritization in patients with neovascular age-related macular degeneration (nAMD)
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