Aflibercept in the Context of AMD Treatment

The switch to aflibercept from other anti-vascular endothelial growth factor (anti-VEGF) agents can improve visual and anatomic outcomes in treatment-resistant cases of age-related macular degeneration (AMD), according to a new report.

Efficacy of Aflibercept in Non-responders

Zois Papadopoulos, MD, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, highlighted the pharmacology, pharmacokinetics, safety, and efficacy of anti-VEGF treatment in AMD. He reviewed the landmark clinical papers that have established these drugs as the standard of care in AMD and told MD Magazine® which parts of his paper were the most interesting.There are a number of reasons that an AMD patient may have failed therapy with aflibercept, such as lesion characteristics, treatment initiation, dosing intervals, or potential tachyphylaxis and genotype risk alleles. One study defined “non-response” as increase in intraretinal/subretinal fluid and/or increasing hemorrhage and/or loss of >5 letters of visual acuity compared to the baseline. From that point, treatment-resistant cases should be reassessed for a different possible diagnosis and switch to other anti-VEGF agents.

Dosage and Administration

But aflibercept is different than other anti-VEGF agents, Papadopoulos wrote. It boasts a higher level of affinity for the VEGF-A factor, a longer intravitreal half-life, and the ability to act as an antagonist for growth factors other than VEGF, such as PIGF. Therefore, he said aflibercept is considered more efficient in therapy of AMD and many clinicians have made the switch from ranibizumab to aflibercept in order to improve their patients’ outcomes.The recommended dose for intravitreal aflibercept is 3 monthly loading injections of 2 mg (0.05 mL) aflibercept followed by 2 mg every second month for the first year until they achieve dryness. The other regimen of administering 2 mg aflibercept every month from the treatment initiation has not been proven more effective than the first method, Papadopoulos wrote.

Whichever treatment protocol is selected, he continued, clinicians and patients need to have discussions and about the goals and benefits of each strategy, including the potential visual acuity gains during and after the first year of treatment.

Switching from Other Anti-VEGF Agents to Aflibercept

Promising Medications

One study Papadopoulos evaluated tested the substitution of pro re nata (PRN) regimen with a treat-and-extend regimen with aflibercept. The study showed that both protocols resulted in stable visual acuity. Treat-and-extend required a larger number of administered injections but fewer visits compared to the PRN strategy.“The most surprising observation I learned was that the switch from other anti-VEGF agents to aflibercept can improve visual and anatomic outcomes in treatment-resistant cases,” Papadopoulos told MD Mag. “Aflibercept is proven in that way to be an effective alternative to other anti-VEGF agents in the management of refractory wet AMD.”Papadopoulos discussed ziv-aflibercept, approved by the FDA for treatment of metastatic colorectal cancer. However, ziv-aflibercept and aflibercept have identical structures, though ziv-aflibercept has a lower cost. Current in vitro and in vivo studies seem to suggest that ziv-aflibercept could be an equally safe, effective, and cheaper alternative to aflibercept.

Papadopoulos also addressed UPARANT, a urokinase receptor-derived peptide inhibitor of VEGF-induced angiogenesis. It is considered a promising approach for the treatment of retinal angiogenesis.

The paper, “Aflibercept: A review of its effect on the treatment of exudative age-related macular degeneration,” was published in the European Journal of Ophthalmology.