Aflibercept Outperforms Bevacizumab at Weaning nAMD Patients Off Treatment

Akrit Sodhi, MD, PhD

Nearly half of patients with wet age-related macular degeneration (AMD) treated with aflibercept could safely stop eye injection therapy after one year without further vision loss, according to new findings from a pilot study.

The report indicated that only 17% of patients with wet AMD treated with another common therapy, bevacizumab, were able to safely halt the drug at the one-year mark.

“Our results suggest that if we can match the right patient to the best therapy, many patients with macular degeneration may not need lifelong therapy,” says Akrit Sodhi, MD, PhD, Associate Professor of Ophthalmology and the Branna and Irving Sisenwein Professor in Ophthalmology at the Wilmer Eye Institute, Johns Hopkins University School of Medicine in a statement. “These results provide additional evidence that aflibercept and bevacizumab should not be considered interchangeable when treating AMD.”

Sodhi noted that the findings built on previous research from Johns Hopkins that reported potentially a third of patients with wet AMD could safely pause therapy after one year of monitoring by a physician

The standard treatment of wet AMD requires monthly or bimonthly eye injections, with aflibercept and bevacizumab being two of the most frequently used in treatment. They can cause discomfort and risk of retinal detachment, injection, and other side effects, as well as a high treatment burden, as patients are required to return to a physician’s office monthly for injections. Often, this can lead to missed treatments and the potential for worsening vision.

Moreover, the interval between treatments for aflibercept (approximately $2,000 per treatment) is longer and may be more effective than bevacizumab (approximately $100 per treatment) in treating wet AMD. However, it remains debated by clinicians whether the nearly 10 times higher cost of monthly aflibercept is justified by this small benefit.

The investigator team from the Wilmer Eye Institute reviewed records of the treatment outcomes of 106 individuals with wet AMD treated between 2013 and 2020 in two locations. Each patient received a monthly injection for the first three months or therapy with either aflibercept or bevacizumab.

During each subsequent visit, investigators evaluated patients and those with inactive wet AMD had the interval between visits extended by two weeks. They noted that if the interval could be safely extended to 12 weeks, treatment was paused and the individuals were closely monitored without treatment.

The study determined a patient was “weaned off” treatment only if they had stable vision and did not require an eye injection for at least 30 weeks following their last treatment during this monitoring period.

Following the three mandatory monthly injections, individuals receiving aflibercept demonstrated a modest advantage over bevacizumab for improvement in vision, which was considered consistent with prior studies, according to investigators.

At the six-month mark, the advantage for monthly injection of aflibercept was no longer observed, they added. However, when the interval between treatments was extended, patients receiving bevacizumab had a higher rate of vision loss than those receiving aflibercept.

Further, at one year, the findings indicate 50% of patients treated with aflibercept were considered weaned off therapy, compared to 17% of patients treated with bevacizumab. Those who still needed treatment saw 44% longer intervals between injections (13.1 weeks vs. 9.1 weeks) for patients treated with aflibercept than those treated with bevacizumab. Each group saw similar rates of fluid accumulation and progressive vision loss.

The findings additionally report the total number of injections for patients treated with aflibercept was reduced by 10% (7.2 vs. 8) over one year when compared with the standard bimonthly treatment schedule. The total injections for those treated with bevacizumab was reduced by 33% (8.7 vs. 12).

Investigators monitored 56 of the 106 patients for an additional year, with 13 of 27 (48%) patients treated with aflibercept remaining off treatment at the end of two years, compared with eight of 29 (28%) patients weaned off bevacizumab. This was considered an improvement over the first year, but was still an inferior result for those receiving aflibercept.

At two years, the number of total injections for patients treated with aflibercept was reduced by 27% (10.2 vs. 14) when compared with the standard bi-monthly treatment schedule, while the total injections for patients treated with bevacizumab was reduced by 44% when compared with the standard monthly treatment schedule.

More research may be required to determine why one drug is more effective than the other, particular as both drugs target the same protein.

The study. “Aflibercept is more effective than bevacizumab at weaning neovascular age-related macular degeneration patients off therapy,” was published in the Journal of Clinical Investigation.