Brolucizumab Shows Promise Over Aflibercept for Diabetic Macular Edema: Insights from a Meta-Analysis
A recent meta-analysis comparing two anti-vascular endothelial growth factor (VEGF) therapies—brolucizumab (Beovu, Novartis) and aflibercept (Eylea, Regeneron Pharmaceuticals)—for the treatment of diabetic macular edema (DME) found that brolucizumab is non-inferior in functional outcomes and superior in anatomic results. The study was led by Leonardo B. Justino, MD, from the Division of Medicine, Federal University of Santa Catarina, Brazil, with contributions from researchers at Tufts Medical Center, Bascom Palmer Eye Institute, and Governador Celso Ramos Hospital.
Challenges with Current Anti-VEGF Treatments
Existing anti-VEGF therapies for DME impose a significant treatment burden, leading to low adherence rates. Factors such as socioeconomic constraints, the ongoing cost, and the frequency of injections contribute to this burden. Patient perceptions, including underestimating the severity of DME or lacking a supportive care network, also play a pivotal role in non-adherence.
This highlights the necessity for anti-VEGF options that provide effective results while requiring fewer clinical visits.
Study Design
The researchers conducted a meta-analysis of randomized controlled trials to evaluate the efficacy and safety of brolucizumab compared to aflibercept. Brolucizumab’s unique properties, including its low molecular weight (26 kDa) and high VEGF-A binding affinity, enable it to deliver molar dosing 11 times higher than aflibercept.
Despite its benefits, intraocular inflammation has been a noted side effect of brolucizumab, particularly in patients treated for neovascular age-related macular degeneration since its approval in 2019.
Data Sources
The investigators reviewed studies from databases including Embase, Cochrane Central Register of Controlled Trials, and PubMed up to February 16, 2024. They analyzed visual, anatomic, and safety outcomes in randomized controlled trials comparing these two therapies for DME.
Key Findings
The meta-analysis included data from 1,253 eyes (57% treated with brolucizumab and 43% with aflibercept) across three trials, with follow-up periods ranging from 52 to 100 weeks.
Functional and Anatomic Outcomes
• Visual Acuity:
Brolucizumab was found to be non-inferior to aflibercept in improving best-corrected visual acuity (LSMD 0.29; 95% CI −1.37 to 1.95; p = 0.73).
• Central Subfield Thickness (CST):
Brolucizumab showed a significantly greater reduction in CST compared to aflibercept (LSMD −24.5 μm; 95% CI −48.2 to −0.7 μm; p < 0.05).
Safety Outcomes
There were no statistically significant differences between the two therapies in the incidence rates of adverse events, including retinal vasculitis or retinal vascular occlusions.
Conclusion
The study demonstrated that while brolucizumab is non-inferior to aflibercept in functional outcomes, it provides superior anatomic benefits for patients with DME. Importantly, the meta-analysis did not observe significant differences in safety profiles between the two therapies.
The authors highlighted the need for new randomized controlled trials with a larger sample size to better assess safety outcomes and solidify brolucizumab's position as an alternative treatment for DME.
This research offers valuable insights into improving therapeutic strategies for DME, paving the way for treatments that are not only effective but also reduce the burden on patients.
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