Effect of Aflibercept (Eylea®) in the Management of Bevacizumab (Avastin®) Resistant Diabetic Macular Edema
Status:
Unknown status
Trial end date:
2017-11-01
Target enrollment:
Participant gender:
Summary
Multicenter randomized trials have demonstrated the safety and efficacy of intravitreal
anti-vascular endothelial growth factor (anti-VEGF) agents for the treatment of diabetic
macular edema. The results are generally good in the short term, with approximately 75% of
patients maintaining or improving vision after initiation of treatment. Despite this
favorable outcome, the observation of persistent fluid is not infrequent during treatment,
even in patients undergoing monthly treatment sessions. Persistent fluid was observed on
optical coherence tomography (OCT) in 70.9% of patients receiving bevacizumab monthly and in
79% of those receiving bevacizumab as needed at the end of the first year in the Comparison
of diabetic macular edema. Treatment Trials. It is possible that resolution of this fluid,
especially when it is centrally located (i.e., foveal), might result in better visual
outcomes.
A drug with higher VEGF-binding affinity may help patients with persistent fluid despite
treatment with bevacizumab. Aflibercept is a new intravitreal VEGF antagonist approved on 28
November 2014 by the Health Canada for the treatment of diabetic macular edema.
In contrast to the antibody-based VEGF binding strategy used by bevacizumab, aflibercept
incorporates the second binding domain of the VEGFR-1 receptor and the third domain of the
VEGFR-2 receptor. By fusing these extracellular protein sequences to the Fc segment of a
human IgG backbone, developers have created a chimeric protein with a very high VEGF binding
affinity. Aflibercept binds all isomers of the VEGF-A family like bevacizumab, but it also
binds VEGF-B and placental growth factors 1 and 2,1,2 which have been both implicated in the
pathogenesis of diabetic retinopathy and of age-related macular degeneration. In addition,
because of the increased trough binding activity and the stronger binding affinity,
aflibercept should be efficacious in neutralizing VEGF more effectively and for longer
duration.