Customized Eye Care: Combined with a T&E regimen, aflibercept promises to revolutionize treatment of retinal diseases

Separate, independent studies suggest that aflibercept has a longer half-life, greater potency, and better VEGF-A binding affinity than other available anti-VEGF agents. It also offers the flexibility to individualize treatment for patients with nAMD and DME, achieving and maintaining robust vision gains with treatment intervals of up to 16 weeks.

A 16-week treat-and-extend (T&E) regimen in the use of aflibercept for retinal disease is possible and could revolutionize treatment options — this good news was presented during the Bayer-sponsored symposium entitled Patient-centric Approaches to Aflibercept Treatment in Retinal Disease at the 38th Asia-Pacific Academy of Ophthalmology Congress (APAO 2023), which recently took place in Kuala Lumpur, Malaysia.

Retinal diseases including neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) can cause irreversible vision loss, leading to blindness. 

Aflibercept, developed by Bayer, is in the vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF) antagonist class of medications. It works by binding to VEGF receptors, stopping abnormal blood vessel growth and leakage in the eyes, and reducing fluid accumulation in the retina. This decreases the risk of macular degeneration and improves vision in patients with nAMD and DME.

Targeting the key drivers of retinal diseases

The effectiveness of aflibercept, also known as Eylea, has been shown to be superior compared to other anti-VEGF agents in the treatment of nAMD and DME. Furthermore, when combined with a T&E regimen, it has the potential to revolutionize the treatment of these conditions.

Before the development of aflibercept, other anti-VEGF agents such as  bevacizumab (Avastin) and ranibizumab (Lucentis) were commonly used to treat nAMD and DME. However, these drugs had limitations, such as short duration of action, variable efficacy, and the need for frequent injections. In contrast, aflibercept has a longer duration of action, with its half-life being nearly twice as long as that of ranibizumab. 

A recent in vitro study reported that aflibercept has a higher potency than brolucizumab and ranibizumab.

“Separate, independent in vitro and in vivo studies suggest that aflibercept has a longer half-life and greater binding affinity for VEGF-A and PLGF than other available anti-VEGF agents,” said Assoc. Prof. Andrew Chang from Sydney Eye Hospital, Sydney Retina Clinic, The University of Sydney, Australia.

Its estimated vitreous half-life is 9.1 to 11 days, while for brolucizumab it is 4.3 to 5.1 days, ranibizumab 7.2 days, bevacizumab 9.8 days, and faricimab 7.5 days.

Aflibercept is the only anti-VEGF agent that inhibits all VEGFR-1 and key VEGFR-2 ligands, including VEGF and PLGF, to target these drivers of retinal damage, Assoc. Prof. Andrew Chang noted.

Individualized patient care 

Patients with nAMD do not benefit equally from anti-VEGF therapy, as there is a spectrum of different needs among patients. The effectiveness of aflibercept can be optimized when combined with a T&E regimen, which cuts the burden of frequent injections on patients. 

In T&E, after an initial period of monthly injections to stabilize the disease, the interval between injections is gradually increased until the maximum interval is reached, after which the patient is monitored.

A pragmatic aflibercept T&E regimen offers the flexibility to achieve and maintain vision gains with intervals of Q4 to Q16, reducing treatment burden, said Prof. Varun Chaudhary from McMaster University, Canada.

Patients with polypoidal choroidal vasculopathy (PCV) can achieve and maintain long-term vision outcomes with aflibercept T&E, similar to patients with nAMD.

Variation in VEGF suppression time between patients indicates a need for treatment individualization. The duration of VEGF-A suppression with aflibercept varies up to 16 weeks in patients with nAMD. “Anti-VEGF treatment burden should be minimized without compromising the patient’s vision,” he said.

According to the Asia-Pacific Vitreo-retina Society’s (APVRS) recommendations: “In the Asia-Pacific region, many patients must commute vast distances to major treatment centers which may adversely affect treatment compliance. T&E retreatment criteria enable interval extension up to Q16 while allowing some stable residual fluid.”

APVRS recommends an interval extension of up to a maximum of 16 weeks with aflibercept, based on the ALTAIR and ARIES studies. This sees six fewer injections with aflibercept versus ranibizumab required to maintain vision gains in nAMD.

In a network analysis, visual outcomes with aflibercept were superior to those reported with ranibizumab. T&E regimen showed significantly superior results over PRN, said Prof. Chaudhary.

In patients treated with aflibercept, there was a statistically significant difference indicating more favorable results for a T&E regimen over a PRN regimen.

The treatment of choice for DME

The VIVID and VISTA trials demonstrated the efficacy of aflibercept in improving visual acuity in patients with DME, and the treatment effect was maintained with a T&E regimen, said Assoc. Prof. Voraporn Chaikitmongkol from Chiang Mai University, Thailand.

“Rapid vision gains achieved with early, intensive aflibercept treatment in year 1 were maintained over 148 weeks, with fewer injections in years 2 and 3,” he presented. Patients from VISTA maintained vision gains up to year 5 with continued aflibercept.

Guidelines from the European Society of Retina Specialists (EURETINA) state that aflibercept is the drug of choice in DME eyes with baseline BCVA below 69 letters, as it shows superiority to bevacizumab over two years and ranibizumab in the first year of treatment.

Aflibercept led to superior vision gains over two years compared with ranibizumab and bevacizumab in patients with baseline VA <69 letters.

One key challenge faced by patients with DME is that working-age patients have a complex comorbidity profile and a high burden of treatment. Diabetic patients with no DME face 14.9 healthcare visit days per year, while DME patients have 25.5 healthcare visit days per year.

“Considering the treatment burden for diabetic patients with a complicated comorbidity profile is critical for disease management,” said Assoc. Prof. Chaikitmongkol.

Clinically meaningful vision gains are achievable with aflibercept regardless of baseline VA, but early, intensive treatment is important to maximize vision gains in all patients, she added.

Evidence from aflibercept clinical trials demonstrates the flexibility of individualized treatment from year 1, with robust vision gains and treatment intervals of up to 16 weeks. Assoc. Prof. Chaikitmongkol also noted that real-world studies show that RCT-like outcomes can be attained in clinical practice with aflibercept.

The flexibility to individualize treatments

Outcomes with aflibercept are reproducible in the clinic, with 10 years of experience and safety data.

“Aflibercept offers the flexibility to individualize treatment for patients with nAMD and DME, achieving and maintaining robust vision gains with treatment intervals up to 16 weeks,” concluded Dr. Kenneth Fong from OasisEye Specialists, Malaysia.

[Editor’s Note: The 38th Asia-Pacific Academy of Ophthalmology Congress (APAO 2023) was held on February 23 to 26 in Kuala Lumpur, Malaysia. Reporting for this story took place during the event.]

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