Laird Harrison

August 11, 2016

SAN FRANCISCO — The reality of anti–vascular endothelial growth factor (anti-VEGF) treatments for neovascular age-related macular degeneration seen in US ophthalmology practices falls far short of the promise of clinical trial results, according to the results of a new analysis.

"In the real world, patients do poorly," Thomas Ciulla, MD, told Medscape Medical News. "It's very concerning. There has to be a better way to address the ocular healthcare of these patients."

The analysis of 750,000 patients is the first large study in the United States of anti-VEGF results outside of randomized, controlled clinical trials, and it echoes the findings from similar European studies, he said.

Dr Ciulla, from the Indiana School of Medicine in Indianapolis and an employee of Ophthotech Corporation, presented the results here at the American Society of Retina Specialists (ASRS) 2016 Annual Meeting.

In clinical trials, three anti-VEGF treatments — ranibizumab (Lucentis, Genentech), bevacizumab (Avastin, Genentech), and aflibercept (Eylea, Regeneron Pharmaceuticals) — have achieved dramatic results. For example, in the MARINA trial, patients receiving monthly injections of ranibizumab 0.5 mg gained a mean of 7.2 letters of vision in 12 months.

But patients and physicians face more challenges outside of the rarefied atmosphere of these trials, said Dr Ciulla.

 
It's very concerning. There has to be a better way to address the ocular healthcare of these patients. Dr Thomas Ciulla
 

"The injections aren't the most comfortable in the world," he explained. "Many patients are elderly," and many have comorbidities that can make it hard to get to an appointment. "Often some adult child has to take time off work to take them to appointments.

"It's almost a capacity issue for doctors' offices, because so many baby boomers have macular degeneration," he added.

To see how well these patients were faring, Dr Ciulla and his colleagues used data from the Vestrum Health Retina Research Dataset.

To be included in the database, patients had to have received at least 3 months of anti-VEGF injections in the first 4 months between January 2011 and July 2013.

The patients' mean age was 82 years at initial presentation. About 70% received bevacizumab. Of the remaining 30%, half received aflibercept and half were given ranibizumab, Dr Ciulla reported.

In general, the results did not differ among the three drugs.

The researchers divided the patients into three cohorts: 97 with records available up to 6 months but not beyond; 195 with records available up to 12 months but not beyond; and 1921 with records available up to at least 24 months. In addition, the researchers stratified the patients by baseline visual acuity.

The 24-month cohort fared best, as did those with the worse visual acuity at baseline.

Table. Change in EDTRS Letters

Baseline Visual Acuity 6-Month Cohort 12-Month Cohort 24-Month Cohort
20/200 +8.8 +8.9 +19.9
20/70 to 20/200 -4.6 -1.3 +2.6
20/40 to 20/70 -1.9 -5.6 -1.2
20/40 or better -5.2 -4.5 -5.2

 

One reason the patients fared worse than patients in clinical trials is that they got far fewer injections, said Dr Ciulla.

The 6-month cohort received a mean of 5.4 injections, the 12-month cohort received 7.3, and the 24-month cohort received 12.1. In contrast, patients in clinical trials have typically gotten one injection per month.

"A take-home point is that we have to be honest with patients that more frequent treatment injections probably give us a better outcome," said Dr Ciulla.

This is probably typical of what is happening throughout the United States, he added, citing a recent survey of ASRS members who found that only 1.5% inject their patients monthly regardless of fluid or examinations.

The largest proportion, 64.8%, treat until patients are dry on optical coherence tomography and then extend a protocol known as "treat-and-extend." Others treat "as needed" or use some combination of as-needed and treat-and-extend.

It is not surprising that the patients with the best visual acuity at baseline fared worse; they had the most to lose, said Dr Ciulla.

"If your vision is good to start, we're not going to make you better. But if your vision is bad, sometimes we can make it better."

However, it's worth remembering that patients with good eyesight would lose even more vision if they were not getting any anti-VEGF treatment, he pointed out. Patients in the MARINA trial who received sham injections lost 10.4 letters in a year.

In studying the 6-month and 12-month cohorts, the researchers surmised that on average, these patients were on a downward trend before they stopped returning for treatment.

That finding could have significance for clinical trials, said Dr Ciulla, because it suggests that patients with some of the lowest scores drop out before the trials finish, which could skew the final results.

The results of this real-world trial don't come as a surprise, given the results of European studies and the challenges faced by clinicians and patients in everyday circumstances, said Jeff Heier, MD, co-president and medical director of Ophthalmic Consultants of Boston.

"A lot of clinicians are hoping that treat-and-extend is going to be a bridge or compromise between monthly therapy and PRN, with less aggressive monitoring," he told Medscape Medical News.

"There are some studies with initially promising results. But treat-and-extend still has to be more carefully studied if we're looking to match the results that many of us have seen in clinical trials."

He said clinicians should treat each patient as an individual, choosing among regimens and sometimes even among different drugs for each.

Dr Ciulla is an employee of Ophthotech. Dr Heier is a consultant for and has received research support from Regeneron and Genentech.

American Society of Retina Specialists (ASRS) 2016 Annual Meeting. Presented August 10, 2016.

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