Treat-and-extend may lead to better AMD results

January 24, 2017
Michelle Dalton, ELS
Michelle Dalton, ELS

Treating neovascular age-related macular degeneration (nAMD) patients with anti-vascular endothelial growth factor (anti-VEGF) ranibizumab (Lucentis, Genentech) on a monthly regimen has produced “great results” in clinical trials, said Prof. Mark C. Gillies, MBBS, PhD. “But what happens after that and what happens in real world practice?”

Treating neovascular age-related macular degeneration (nAMD) patients with anti-vascular endothelial growth factor (anti-VEGF) ranibizumab (Lucentis, Genentech) on a monthly regimen has produced “great results” in clinical trials, said Prof. Mark C. Gillies, MBBS, PhD. “But what happens after that and what happens in real world practice?” 

Dr. Gillies pointed out that early results have not been promising, with almost all eyes developing macular atrophy, and losing vision compared to baseline over the long term. He said that starting treatment earlier is better, adding to the growing literature on the topic.  

“We know that atrophy is natural part of the disease,” said Dr. Gillies of the University of Sydney, Australia. “All patients will get it if they live long enough, but we also know from the Comparison of AMD Treatment Trial (CATT) and The UK Inhibition of VEGF in Age-related choroidal Neovascularization (IVAN) studies that the eyes that were treated frequently in these studies had a greater incidence of development of new macular atrophy.” 

The Fight Retinal Blindness! (FRB) database identified 1,212 eyes of 1,048 patients who were treatment-naïve when they started 5 years previously and were treated in Australia, New Zealand, and Switzerland, predominantly with ranibizumab, but a few were treated with bevacizumab. By year 5, data was available on 549 eyes, and by year 7, data was available on 131 eyes.

Study outcomes

The shorter long-term outcomes were positive, with the mean visual acuity gain after 5 years at 0.7 ETDRS letters, with 43% of the eyes having a visual acuity of at least 70 letters or better. However, vision did wane with time, mimicking the decline in effect from other long-term studies.

After 7 years, the FRB cohort had lost 2.8 letters, which compares favorably to the SEVEN-UP extension study which reported an overall 8.6-letter decline over an average 7.3 years of follow-up. In the CATT analysis, the overall loss of letters at 5 years was 3.3, Dr. Gillies said.

“We also found that the eyes that started with good vision didn’t improve but they retained good vision,” Dr. Gillies said. “Whereas eyes that had poor vision at baseline (35 letters or worse) had good improvements but they still couldn't see very well.”

 

20/40 or better indicator

A “better indication” of how patients’ vision truly is may be the proportion of eyes that achieve 20/40 or better, Dr. Gillies said. Using that criterion, after 7 years, 23% of eyes in SEVEN-UP achieved 20/40 or better compared to 40% in the FRB cohort.

Conversely, after 7 years, 37% of eyes in SEVEN-UP were 20/200 or worse compared to only 18% in the FRB cohort. In SEVEN-UP, cohorts were treated on a PRN regimen, with patients receiving about 2 injections per year after year 4 through to year 7.

“In our cohort, the patients received 5 injections a year from year 2 through year 7,” Dr. Gillies said.

The safety was acceptable, with the risk of hemorrhage per injection at 0.11%, the risk rate of infectious endophthalmitis at 0.04%, non-infectious endophthalmitis at 0.01%, retinal detachment at 0.02%, and retinal epithelium tear at 0.04%.

There were several causes attributed to the loss of 10 letters or more from baseline to 6.5+ years, he said. Although 40% of the eyes developed geographic atrophy in the FRB study, “the others had conditions which may have been a result of under-treatment,” Dr. Gillies added.

For example, 11 patients (33%) had subretinal fibrosis, 4 patients (12%) had structural damage (loss of ellipsoid), 2 patients each (6%) had infectious endophthalmitis, unoperated cataract, or active lesion, and 1 patient (3%) had retinal pigment epithelial rip, Dr. Gillies said.

 

Regional differences

Regional differences may have accounted for some of the variability. “We don’t have many restrictions in Australia,” Dr. Gillies said. Plus, “we can usually arrange for the eyes to be treated within an hour of diagnosis.”

Adding to the differences among the practitioners is that “most of ours use treat-and-extend regimens” instead of PRN, which may be the reason for the better outcomes.

“Future investigations will need to consider factors, such as baseline visual acuity and treatment intensity when reporting and comparing outcomes,” he said.

 

 

Mark C. Gillies, MBBS, PhD

E: mark@eye.usyd.edu.au

This article was adapted from a presentation that Dr. Gillies delivered at the Retina Subspecialty Day before the 2016 American Academy of Ophthalmology annual meeting. Dr. Gillies is a consultant to Allergan, Bayer Healthcare, Novartis, and Opthea