A meta-analysis comparing brolucizumab (Beovu, Novartis) and aflibercept (Eylea, Regeneron Pharmaceuticals) in treating diabetic macular edema (DME) reveals that brolucizumab is non-inferior in functional outcomes and superior in anatomic parameters. The study, led by Leonardo B. Justino from the Federal University of Santa Catarina, highlights the potential of brolucizumab as an alternative treatment for DME, addressing the need for therapies with longer durations between clinical visits and improved patient outcomes.
Addressing Treatment Burden in DME
Current anti-VEGF treatments for DME often present a high treatment burden, leading to poor adherence. Socioeconomic constraints, the cost and frequency of injections, and patient perceptions regarding the severity of DME all contribute to this challenge. The meta-analysis aimed to evaluate the efficacy and safety of brolucizumab compared to aflibercept, seeking a therapy that reduces the burden while maintaining effectiveness.
Study Design and Methods
The meta-analysis included data from 1,253 patients (1,253 eyes) across three randomized controlled trials, with 57% treated with brolucizumab and 43% with aflibercept. The study searched Embase, Cochrane Central Register of Controlled Trials, and PubMed databases up to February 16, 2024. The mean follow-up times ranged from 52 to 100 weeks.
Key Findings: Visual Acuity and Anatomic Improvements
The results indicated that brolucizumab was non-inferior to aflibercept in terms of the mean change in best-corrected visual acuity from baseline (least squares mean difference [LSMD] 0.29; 95% confidence interval [CI] −1.37 to 1.95; p = 0.73). Importantly, the change in central subfield thickness was significantly greater in the brolucizumab group compared to the aflibercept group (LSMD −24.5 μm; 95% CI −48.2 to −0.7 μm; p < 0.05).
Safety Profile
The meta-analysis found no statistically significant differences in the incidence rates of adverse events between the two drugs, including retinal vasculitis or retinal vascular occlusions. This is a notable finding, as previous studies had raised concerns about intraocular inflammation associated with brolucizumab.
Mechanism of Action and Dosing
Brolucizumab is a single-chain variable fragment with a high binding affinity for VEGF-A isoforms. Its low molecular weight (26 kDa) allows for a molar dosing delivery 11 times higher than aflibercept. This unique characteristic potentially contributes to its efficacy in improving anatomic outcomes.
Implications for DME Treatment
The study concludes that brolucizumab significantly improves anatomic parameters in patients with DME while maintaining non-inferiority in functional outcomes compared to aflibercept. The authors emphasize the need for further randomized controlled trials powered to assess safety outcomes to solidify brolucizumab's role as an alternative treatment for DME.
