Comparative efficacy of intravitreal anti-VEGF therapy for neovascular age-related macular degeneration: A systematic review with network meta-analysis

The aim of this review was to evaluate the comparative efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular AMD. We searched 12 literature databases for randomised clinical trials (RCT) on anti-VEGF therapy for neovascular AMD and extracted data on: change from baseline to 12 months in best-corrected visual acuity (BCVA) and central retinal thickness (CRT), and cumulative number of injections at 12 months. The reference for comparison was monthly ranibizumab. Comparisons were made using network meta-analyses. Forty-nine RCTs including 23 257 eyes of 23 257 patients were included. No anti-VEGF drug or treatment regimen provided a better BCVA response compared to the reference. For CRT, small but statistically significant improvements over the reference were observed for brolucizumab 3 mg (-27.9 μm) or 6 mg (-38.1 μm) in loading dose (LD) then every 8-12 weeks, aflibercept 8 mg in LD then every 12 (-26.9 μm) or 16 weeks (-32.1 μm), faricimab 6 mg in LD then treat-and-extend (-18.1 μm) and aflibercept 2 mg in LD then every 8 weeks (-11.3 μm). For the cumulative number of injections, a range of anti-VEGF drugs and treatment regimens provided a statistically significant and clinically meaningful reduction compared to the reference. When results are considered simultaneously, faricimab 6.0 mg or aflibercept 8.0 mg in a treatment regimen with an LD followed by either a treat-and-extend regimen or a fixed 12- or 16-week regimen appears to provide the optimal balance between visual outcomes, anatomical outcomes and the lowest treatment burden. However, studies of the long-term efficacy of newer anti-VEGF drugs are warranted.