Which DME Drug to Try First? Patients on Bevacizumab Can Successfully Transition to Aflibercept

Study findings presented at a session at the American Academy of Ophthalmology (AAO) 2022 conference in Chicago, Illinois, showed that outcomes in eyes treated for moderate vision loss due to center-involved diabetic macular edema (CI-DME) were similar over 2 years, whether the patients were treated first with aflibercept alone or with the administration of bevacizumab first plus a switch to aflibercept therapy.

Starting patients on bevacizumab before switching to aflibercept if there was a suboptimal response was safe and effective, the study found.

The study was presented by Chirag Jhaveri, MD, an affiliate faculty member in the Department of Ophthalmology at Dell Medical School at the University of Texas in Austin. The retina specialist is also vice chair for the Diabetic Retinopathy Clinical Research network (DRCR.net), which presented the research results Saturday. The study findings were published in the New England Journal of Medicine in August.

A previous study by the same research group, Protocol T, found that eyes with a visual acuity (VA) of 20/50 or worse had better visual outcomes after aflibercept treatment through 2 years when compared with eyes treated with bevacizumab (mean improvement of 18.1 vs 13.3 ETDRS [Early Treatment of Diabetic Retinopathy Study] letters) and had better vision through 1 year compared with patients on ranibizumab.

Many patients with 20/50 vision or worse who were treated with bevacizumab had good visual outcomes as well, with 68% achieving a final VA of 20/40 or better after 2 years.

The Saturday presentation focused on the Protocol AC trial, which looked at whether step therapy, where payers require the less expensive drug first, had an impact on visual outcomes. Did patients starting on bevacizumab and switching to aflibercept face compromises in their long-term VA compared with patients strictly on aflibercept monotherapy?

Bevacizumab is often more available and widely used outside of the United States, noted Jhaveri.

“Step therapy is where patients are forced to use a certain medication before the physician can use another medication usually secondary to cost,” he said. “And so in this situation, for example, bevacizumab, which is off-label, is often required for us to use before we have the opportunity to use aflibercept, which is on-label.”

The randomized multicenter clinical trial enrolled 312 eyes. Patients were included if they aged 18 years and older and had type 1 or type 2 diabetes. Patients needed to have vision of 20/50 or worse. They could have had previous anti–vascular endothelial growth factor (VEGF) injections but it could not have been within 12 months. Other treatments for DME could not have been taken within 4 months.

The patients were split into 2 groups, where 1 group had aflibercept alone and the other group was started on bevacizumab. Patients in the bevacizumab group could switch to aflibercept at and after 12 weeks if they had persistent CI-DME, had an injection with bevacizumab given at the last 2 visits, eye had not improved by at least 5 letters over the previous 2 visits, central subfield thickness (CST) had not improved by 10% or more over the past 2 visits, and vision was worse than 20/50 before 24 weeks had elapsed or 20/32 or worse 24 weeks or later.

“And the rationale for [switching medicine if patients had 20/32 vision or worse] is that maybe there were some patients who improved a little bit on bevacizumab first but plateaued. Could switching them to aflibercept allow for additional vision gains?” said Jhaveri.

Patients who were switched to aflibercept were given at least 2 injections before resuming treatment guidelines. There were 6 monthly injections, except for eyes where VA of 20/20 was achieved along with a CST less than the prespecified threshholds, as well as stable VA and CST.

There were 158 patients who started with aflibercept monotherapy and 154 who started with bevacizumab. Both groups were 48% female and the median age was 60 and 61 years respectively. White participants made up 52% and 54% of each respective group. Patients on bevacizumab had about 1 1/2 more injections on average compared with those on aflibercept. Baseline characteristics were similar in each group, with 16% and 19% of the groups having prior intravitreal anti-VEGF treatment for DME.

Most of the patients who had bevacizumab first (70%) met the switch criteria for aflibercept by the end of the 2-year period compared with 30% of the patients on aflibercept monotherapy.

VA after 2 years was similar in both groups as 22% of both groups had vision of 20/20 or better (adjusted difference, –1%; 95% CI, –11% to 8%); 73% of the aflibercept group and 74% of the bevacizumab-first group had VA of 20/40 or better (adjusted difference, –7%; 95% CI, –19% to 5%).

Only 5% of the aflibercept group and 2% of the bevacizumab first group had VA of 20/200 or worse (adjusted difference, 3%; 95% CI, –1% to 7%).

Although aflibercept performed better than bevacizumab within the first year of treatment, both medications performed similarly across 2 years, with CST reduced in both treatments. In the aflibercept group, 60% of the participants had resolved CI-DME compared with 55% of the bevacizumab group.

The study did not include any anti-VEGF agents other than aflibercept that were FDA-approved for treatment of DME, which was a significant limitation. Serious adverse events and hospitalizations for adverse events were more common in the aflibercept-only group.

“Initiating therapy with bevacizumab and switching to aflibercept that's done in this trial is a safe and effective alternative to aflibercept monotherapy in eyes with moderate vision loss due to center-involved DME,” said Jhaveri.

Reference

Jhaveri CD, Glassman AR, Ferris FL, et al; DRCR Retina Network. Aflibercept monotherapy or bevacizumab first for diabetic macular edema. N Engl J Med 2022;387:692-703. doi:10.1056/NEJMoa2204225

Allison Inserro contributed to this report.