A researcher from Johns Hopkins Medicine helped lead colleagues from across the country in a government-sponsored study by the Diabetic Retinopathy Clinical Research Network to discover that three drugs -- Eylea, Avastin and Lucentis -- used to treat diabetic macular edema are all effective. They also discovered that Eylea outperformed the other two drugs when vision loss was moderate to severe.
Prior to this study, which will be published in the Feb. 18 issue of the New England Journal of Medicine, it was not known how the efficacy or safety of the three drugs compared.
"These findings will equip patients with the information they need to discuss with their doctors which drug to choose and will help guide protocols for clinicians using these drugs to treat patients with diabetic macular edema," says Neil Bressler, M.D., past chair of the Diabetic Retinopathy Clinical Research Network and director of the Retina Division at Johns Hopkins Medicine.
There are nearly 750,000 people in the U.S. affected by diabetic macular edema, a diabetes-related eye disease that causes vision loss. About one-quarter of those people may have moderate to severe vision loss from diabetic macular edema when they see an ophthalmologist. In fact, it is a leading cause of vision loss in working-age Americans and is becoming a major global public health issue. Diabetic macular edema affects the area of the eye that is used for reading, driving and watching television ? all common functions of daily living.
"Vision loss can be debilitating and isolating, especially for those who, in addition to vision loss, have the responsibility of managing diabetes. Discovering the best ways to prevent and treat vision loss is critical to a patient's quality of life," says Bressler. "We wanted to do our part by providing scientific comparative data to help patients and clinicians make more informed health decisions."
Investigators enrolled 660 people with diabetic macular edema at 88 clinical trial sites across the United States. When the study began, participants were 61 years old on average and had type 1 or type 2 diabetes for 17 years on average. Only people with a visual acuity of 20/32 or worse were eligible to participate. (To see clearly, a person with 20/32 vision would have to be 20 feet away from an object that a person with normal vision can see clearly at 32 feet. At 20/40, 3 lines worse than 20/20, the letters are twice as big as they are on the 20/20 line.) At enrollment, about half the participants had 20/32 or 20/40 vision, and the other half had 20/50 or worse vision. In many states, a corrected visual acuity of 20/40 or better in at least one eye is required for a driver's license that allows both day- and nighttime driving.
Each participant was randomly assigned to receive Eylea (2 milligrams/0.05 milliliter), Avastin (1.25 milligrams/0.05 milliliter) or Lucentis (0.3 milligrams/0.05 milliliter). Participants were evaluated monthly and received the assigned study drug by injection directly into the eye until the diabetic macular edema resolved or stabilized. Additionally, laser treatment was given if diabetic macular edema persisted without continual improvement after six months of injections. Laser surgery used to be the only treatment for diabetic macular edema until the widespread adoption of Eylea, Avastin and Lucentis a few years ago.
All three drugs target a substance called vascular endothelial growth factor (VEGF), which can cause leakage from blood vessels and the growth of new, abnormal blood vessels. Anti-VEGF drugs work for diabetic macular edema by reducing vascular leakage.
Based on Medicare allowable charges, the per-injection costs of each drug at the doses used in this study were about $1,960 for Eylea, about $70 for Avastin and about $1,200 for Lucentis. During the yearlong study, participants on Avastin and Lucentis received, on average, 10 injections, versus nine for those on Eylea.
One year after starting treatment, vision had improved substantially for the majority of trial participants. When visual acuity was 20/32 or 20/40 at the start of the trial, vision improved on average almost two lines on an eye chart in all three treatment groups. In contrast, for participants whose visual acuity was 20/50 or worse at the start of the trial, Eylea improved vision on average almost four lines, Avastin improved vision on average almost 2.5 lines and Lucentis improved vision on average almost three lines. At least 50 percent more people given Eylea compared with Avastin improved by three or more lines on the eye chart, and at least 30 percent more people given Eylea compared with Lucentis improved by three or more lines on the eye chart.
All three drugs reduced swelling of the macula, but Eylea and Lucentis reduced the swelling more than Avastin. Also, during the study, a smaller percentage of participants on Eylea (36 percent) underwent laser treatment for persistent edema that did not resolve with anti-VEGF treatment alone, compared with those on Avastin (56 percent) or Lucentis (46 percent).
The trial was funded by the National Eye Institute, part of the National Institutes of Health, for grants EY14231, EY14229 and EY18817.
Eylea and Lucentis were provided by drug manufacturers Regeneron and Genentech, respectively. Additional research funding for this study was provided by the National Institute of Diabetes and Digestive and Kidney Diseases, also a part of the National Institutes of Health.