Efficacy and Safety of Anti–Vascular Endothelial Growth Factor Monotherapies for Neovascular Age-Related Macular Degeneration: A Mixed Treatment Comparison

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.

Biomimetic, Injectable, and Self-Healing Hydrogels with Sustained Release of Ranibizumab to Treat Retinal Neovascularization

“…Nowadays, a few anti-VEGF drugs (e.g., ranibizumab, a monoclonal antibody fragment targeting VEGF-A) have been used in clinical settings to treat RNV, which is most widely used for the treatment of RNV, approved by the U.S. Food and Drug Administration (FDA). − Many investigations have demonstrated that the effects of ranibizumab as an up-and-coming RNV treatment are superior to laser treatment with fewer complications . However, ranibizumab has a short half-life (approximate 7 days on average), and sometimes, to achieve a certain therapeutic effect, repeated and frequent intravitreal injections are required, leading to a higher rate of complications such as subconjunctival hemorrhage, increased intraocular pressure, vision-threatening endophthalmitis, and retinal detachment. − A variety of complications and increased costs lead to decreased patient compliance, and treatment is often interrupted.…”

The Efficacy and Safety of Brolucizumab for the Treatment of nAMD: A Systematic Review and Meta-Analysis

“…2013;ClinicalTrials.gov, 2015;ClinicalTrials.gov, 2016;ClinicalTrials.gov, 2017;ClinicalTrials.gov, 2020;ClinicalTrials.gov, 2021). Two large studies, HAWK and HARRIER, demonstrated non-inferiority of brolucizumab and an overall safety profile similar to that of aflibercept (Zhang et al, 2021). However, given the different control drugs, dosages, and administration durations of the aforementioned randomized controlled trials, a comprehensive meta-analysis was valuable to evaluate the subtle differences between efficacy and safety of brolucizumab and other anti-VEGF drugs.…”

Innovations in Diabetic Macular Edema Management: A Comprehensive Review of Automated Quantification and Anti-vascular Endothelial Growth Factor Intervention

“…These drugs function by inhibiting the activity of VEGF, a pivotal factor in angiogenesis and vascular permeability, thereby reducing macular edema and enhancing visual acuity for patients with these conditions [ 35 , 38 , 37 ]. Research studies indicate that the efficacy of anti-VEGF drugs varies based on the specific drug, dosage, and therapeutic strategy employed [ 35 , 39 ]. For instance, aflibercept has demonstrated greater blocking potency than ranibizumab or bevacizumab [ 35 ].…”

“…Despite these findings, controversies persist regarding the ideal drug and optimum therapeutic strategy. Challenges arise in acquiring comparative efficacy and safety profiles from current trials due to many therapeutic regimens involving anti-VEGF therapy, encompassing different drugs, dosages, and therapeutic approaches [ 39 ]. While anti-VEGF therapies effectively address various ocular conditions, the varying efficacy and safety profiles of different drugs, dosages, and therapeutic strategies highlight the need for further research to determine the optimal treatment approach tailored to individual patients.…”