Anti-vascular endothelial growth factor for neovascular age-related macular degeneration: a meta-analysis of randomized controlled trials

Abstract

Background: To evaluate the relative efficacy and safety of anti-vascular endothelial growth factor (anti-VEGF) agents for the treatment of neovascular age-related macular degeneration (AMD).

Methods: Systematic literature review identifying RCTs comparing anti-VEGF agents to another treatment published before June 2016. Efficacy assessed by mean change in best corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline at up to 2 years followup. Safety assessed by proportions of patients with death, arteriothrombotic and venous thrombotic events, and at least one serious systemic adverse event at up to 2 years of followup.

Results: Fifteen RCTs selected for meta-analysis (8320 patients). Two trials compared pegaptanib, and three trials compared ranibizumab versus control. Eight trials compared bevacizumab with ranibizumab. Two trials compared aflibercept with ranibizumab. There were no significant differences between bevacizumab and ranibizumab for BCVA at 1 or 2 years (weighted mean difference = - 0.57, 95% CI - 1.55 to 0.41, P = 0.25 and weighted mean difference = - 0.76, 95% CI - 2.25 to 0.73, P = 0.32, respectively). Ranibizumab was more effective in reducing CMT at 1 year (weighted mean difference = 4.49, 95% CI 1.13 to 7.84, P = 0.009). Risk ratios comparing rates of serious systemic adverse events at 1 and 2 years were slightly out of favour for bevacizumab. Aflibercept compared with ranibizumab demonstrated similar mean change in BCVA, reduction in CMT, and safety at 1 year.

Conclusions: Bevacizumab and ranibizumab had equivalent efficacy for BCVA, while ranibizumab had greater reduction in CMT and less rate of serious systemic adverse events. Aflibercept and ranibizumab had comparable efficacy for BCVA and CMT. This provides information to balance comparable effects on vision and risk of adverse events between anti-VEGF agents.

Keywords: Anti-vascular endothelial growth factor; Meta-analysis; Neovascular age-related macular degeneration; Randomized controlled trials.

Fig. 1

Flow diagram of studies included in this meta-analysis. ^*Studies followed patients for less than one year; trials of different drug doses compared with each other, with no control or comparator; studies used drugs in combination with other treatments

Fig. 2

Risk of bias assessment of included studies. ⁺Low risk,^?Unclear risk, ⁻High risk

Fig. 3

Mean change in best corrected visual acuity (in letters) from baseline comparing bevacizumab with ranibizumab at 1 and 2 years. IV, inverse variance; SD, standard deviation

Fig. 4

Mean change in central macular thickness (μm) from baseline comparing bevacizumab with ranibizumab at 1 and 2 years. IV, inverse variance; SD, standard deviation

Fig. 5

Serious systemic adverse events comparing bevacizumab with ranibizumab at 1 year. M-H, Mantel–Haenszel statistics

Fig. 6

Serious systemic adverse events comparing bevacizumab with ranibizumab at 2 years. M-H, Mantel–Haenszel statistics

Fig. 7

Ranibizumab versus control. Mean change in best corrected visual acuity (in letters) from baseline comparing ranibizumab with control at 1 and 2 years. IV, inverse variance; SD, standard deviation

Fig. 8

Aflibercept versus ranibizumab. Mean change in best corrected visual acuity (in letters) from baseline comparing aflibercept with ranibizumab at 1 year. IV, inverse variance; SD, standard deviation

Fig. 9

Aflibercept versus ranibizumab. Mean change in central macular thickness (μm) from baseline comparing aflibercept with ranibizumab at 1. IV, inverse variance; SD, standard deviation

Fig. 10

Ranibizumab versus control. Serious systemic adverse events comparing ranibizumab with control at 1 year. M-H, Mantel–Haenszel statistics

Fig. 11

Ranibizumab versus control. Serious systemic adverse events comparing ranibizumab with control at 2 years. M-H, Mantel–Haenszel statistics

Fig. 12

Aflibercept versus ranibizumab. Serious systemic adverse events comparing aflibercept with ranibizumab at 1 year. M-H, Mantel–Haenszel statistics