The early advantage aflibercept showed in treating patients with diabetic macular edema (DME) narrowed after 2 years of treatment, according to follow-up data from the Diabetic Retinopathy Clinical Research Network (DRCR.net) Protocol T study.
One-year results from Protocol T showed that aflibercept may be more effective than bevacizumab and ranibizumab in patients with worse baseline visual acuity. But 2-year data published last week shows ranibizumab is as effective as aflibercept. Aflibercept continued to show an advantage over bevacizumab (P=0.02).
The multicenter, randomized trial known as Protocol T evaluated the relative effectiveness and safety of intravitreal aflibercept, bevacizumab and ranibizumab in 660 patients with center-involving DME. All subjects were treated monthly until the disease stabilized, followed by PRN treatment.
Similar to year-1 results, all 3 anti-VEGF therapies improve vision in patients with mild vision loss (20/32 to 20/40) at baseline. But in patients with 20/50 or worse baseline vision, the superiority of aflibercept over ranibizumab was no longer identified at 2 years (18.1 vs. 16.1 letters, P=0.18). Mean improvement in the bevacizumab group was 13.3 letters at 2 years.
Encouragingly, the number of injections required in year 2 decreased in all 3 groups, dropping from an average of 9 injections to just 5. Supplemental laser photocoagulation was highest among those in the bevacizumab group (64%), followed by ranibizumab (52%) and aflibercept (41%).
“This rigorous trial confirms that Eylea, Avastin, and Lucentis are all effective treatments for diabetic macular edema,” said Paul A. Sieving, MD, PhD, director of NIH’s National Eye Institute, which funded the trial. “Eye care providers and patients can have confidence in all three drugs.”
Dr. John Wells, lead investigator, says that even though ranibizumab catches up, he won’t be changing his treatment approach. Why withhold the better treatment for a year and a half, he questions.
Although this study was not powered to detect differences in safety, the risk of heart attack, stroke or death from a cardiovascular condition was significantly higher in ranibizumab-treated patients compared with aflibercept (P=0.047) at 2 years. Because no previous studies detected such a safety signal, Dr. Wells says this data would not deter him from prescribing ranibizumab in his patients.
However, this safety data does concern some retina specialists who point out that diabetics have compromised systemic VEGF levels, unlike patients with wet AMD.
Bevacizumab is way ahead of the others in cost-effectiveness. Aflibercept, reimbursed by Medicare at about $1,850 an injection, is significantly more expensive than ranibizumab, at $1,200 a shot, or bevacizumab, at $60 per dose.