Comparative Safety of Bevacizumab, Ranibizumab, and Aflibercept for Treatment of Neovascular Age-Related Macular Degeneration (AMD): A Systematic Review and Network Meta-Analysis of Direct Comparative Studies

Abstract

Background: Since the efficacy of ranibizumab (RBZ), bevacizumab (BVZ) and aflibercept (AFB) is comparable in neovascular age-related macular degeneration (AMD), we conducted a systematic review and meta-analysis to evaluate the long-term safety profiles of these agents, including ocular safety. Methods: Systematic review identifying randomized controlled trials (RCTs) comparing RBZ, BVZ and AFB directly published before March 2019. Serious ocular adverse events (SOAE) of special interest were endophthalmitis, pseudo-endophthalmitis, retinal pigment epithelium tear and newly identified macular atrophy. Results: Thirteen RCTs selected for meta-analysis (4952 patients, 8723 people-years follow-up): 10 compared RBZ vs. BVZ and three RBZ vs. AFB. There were no significant differences in almost all adverse events (systemic and ocular) between BVZ, RBZ and AFB in up to two years’ follow-up. Macular atrophy was reported heterogeneously and not reported as SOAE in most trials. Conclusions: Direct comparison of RBZ, BVZ and AFB safety profiles in the RCT network meta-analytical setting have not revealed a consistent benefit of these three commonly used anti-vascular endothelial growth factor (anti-VEGF) agents in AMD. Network model ranking highlighted potential benefits of RBZ in terms of a systemic safety profile; however, this appears a hypothesis rather than a conclusion. Newly identified macular atrophy is underestimated in RCTs—future real-world data should be focused on SOAE.

Neovascular Macular Degeneration: A Review of Etiology, Risk Factors, and Recent Advances in Research and Therapy

“…Pluykhova et al compared the safety profile of long-term use of ranibizumab, bevacizumab, and aflibercepts in the RCT (randomized clinical trial) meta-analysis, with the study hypothesizing the potential benefits of ranibizumab vs. bevacizumab in terms of a systemic safety profile. However, more direct RCT on ocular safety needs to be conducted to validate these findings further [ 242 ].…”

Progression from Type 2 Macular Neovascularization to Fibrovascular Pigment Epithelial Detachment

“…Over the last few decades, anti-VEGF therapy has revolutionized the treatment of several retinal diseases. To date, anti-VEGF intravitreal injection is the most commonly performed ophthalmic procedure for the treatment of different retinal diseases such as neovascular AMD, diabetic retinopathy, retinal vein occlusion and secondary neovascularization in tumoral or inflammatory diseases [4][5][6][7][8].…”

“…In neovascular AMD, it has been shown that functional prognosis worsens if treatment by anti-VEGF intravitreal injections is delayed and strongly correlates with visual acuity at the time of the first injection [9]. Various molecules are available (ranibizumab, aflibercept and bevacizumab) and all have been proven to be safe and efficient for controlling MNV [4].…”

TGF-β Serum Levels in Diabetic Retinopathy Patients and the Role of Anti-VEGF Therapy

“…Aflibercept is a human recombinant fusion protein that acts as a soluble decoy receptor for VEGF family members, including VEGF-A, VEGF-B and placental growth factor (PlGF) [ 9 , 10 ]. Aflibercept is approved with the following indications: neovascular age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema and diabetic retinopathy [ 11 , 12 ]. Furthermore, aflibercept exerts in vitro and in vivo anti-inflammatory action, modulating the phosphorylation of extracellular signal-regulated kinases (ERK) and decreasing retinal tumor necrosis factor alpha (TNF-α) release [ 13 ].…”