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Anti-VEGFs improve vision at 2 years in eyes with diabetic macular edema
DRCR.net Protocol T study showed that aflibercept was superior to ranibizumab at 1 year but not at 2 years.
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Three anti-VEGFs with a standardized follow-up and re-treatment regimen improved visual acuity at 2 years in eyes with diabetic macular edema, according to a study.
The Diabetic Retinopathy Clinical Research Network Protocol T study compared the effectiveness of Eylea (aflibercept, Regeneron), Avastin (bevacizumab, Genentech) and Lucentis (ranibizumab, Genentech) in the treatment of center-involved DME associated with visual impairment.
The injection protocol also significantly reduced the treatment burden.
“I think the most important finding from the second year was that all three drugs continued to show very effective gains in vision,” John A. Wells, MD, the lead author, told Ocular Surgery News. “The maintenance of these vision gains was achieved with roughly 40% fewer injections compared to the first year and with fewer lasers compared to the first year.”
Patients and injections
The study, published in Ophthalmology, included 660 patients with visual acuity impairment related to center-involved DME.
Eyes were assigned randomly 1:1:1 to receive intravitreal injections of aflibercept 2 mg, bevacizumab 1.25 mg or ranibizumab 0.3 mg.
Patients were examined every 4 weeks in the first year and every 4 weeks to 16 weeks in the second year. Focal/grid laser photocoagulation was performed after 6 months in cases in which DME persisted.
Median number of injections in year 2 was five in the aflibercept group, six in the bevacizumab group and six in the ranibizumab group. Mean number of injections over 2 years was 15 in the aflibercept group, 16 in the bevacizumab group and 15 in the ranibizumab group.
Focal/grid laser photocoagulation was performed at least once in 41% of eyes in the aflibercept group, 64% in the bevacizumab group and 52% in the ranibizumab group over 2 years.
Outcomes
Comparing all 660 eyes enrolled in the study, visual acuity improved by 12.8 letters in the aflibercept group, 10 letters in the bevacizumab group and 12.3 letters in the ranibizumab group at 2 years. The difference between the aflibercept and bevacizumab groups was statistically significant (P = .02). However, this overall comparison has limited clinical utility because the interaction with baseline visual acuity seen at 1 year persisted at the 2-year final study endpoint, according to Wells.
Mean improvement in eyes with baseline visual acuity of 20/50 to 20/320 was 18.1 letters in the aflibercept group, 13.3 letters in the bevacizumab group and 16.1 letters in the ranibizumab group at 2 years. The difference between the aflibercept and bevacizumab groups was statistically significant (P = .02), but there was no difference between aflibercept and ranibizumab, or ranibizumab and bevacizumab.
Mean improvement in eyes with baseline visual acuity of 20/32 to 20/40 was 7.8 letters in the aflibercept group, 6.8 letters in the bevacizumab group and 8.6 letters in the ranibizumab group. The between-group differences were not statistically significant.
“There was this really strong interaction seen with the baseline visual acuity such that if the baseline acuity was 20/40 to 20/32, there was no difference in vision improvement between the three drugs,” Wells said. “What you’ve got statistically at the 2-year endpoint was that aflibercept was still superior to bevacizumab but not ranibizumab. Aflibercept was still superior to bevacizumab at the 2-year endpoint, just as it was at 1 year, but at 2 years aflibercept was no longer superior to ranibizumab. It was at 1 year but not at 2 years.”
The rate of cardiovascular events was 5% in the aflibercept group, 8% in the bevacizumab group and 12% in the ranibizumab group; the difference was significant between the aflibercept and ranibizumab groups (P = .047).
“That was a really unexpected finding,” Wells said. “We’re not sure what to make of it. We think it may be a chance finding, and we think it requires more study.”
Wells said he would choose aflibercept over ranibizumab in eyes with worse baseline vision, even though the two drugs are similarly effective at 2 years.
“I don’t think you want to give up the early benefit of aflibercept just because ranibizumab catches up at 2 years, so I continue to recommend Eylea for eyes with worse vision,” Wells said. – by Matt Hasson
- Reference:
- Wells JA, et al. Ophthalmology. 2016;doi:10.1016/j.ophtha.2016.02.022.
- For more information:
- John A. Wells, MD, can be reached at Palmetto Retina Center, 2750 Laurel St., Suite 101, Columbia, SC 29204; email: jackwells@palmettoretina.com.
Disclosure: Wells reports he is an investigator for Genentech and Regeneron.
Perspective
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Marco Zarbin, MD, PhD
Among patients with baseline best corrected visual acuity of 20/50 or worse, aflibercept gave superior visual results at year 1, but by year 2, there was no statistically significant difference in visual outcome gains between aflibercept and ranibizumab, nor was there a clinically important difference in visual outcome for any of the three agents. The latter result implies that the difference in mean visual outcome gains between aflibercept and bevacizumab at year 2, although statistically significant, is not clinically important as implied by the investigators themselves. Based on what we learned from Protocol I, it is unlikely that laser had an important impact on vision at year 2 of this study.
The treatment paradigm in Protocol T is heavily OCT driven. In all three treatment cohorts, injections were required in both year 1 and year 2 for more than 80% of patients. There was neither a statistically significant nor a clinically important difference in the median number of injections given for each of the agents during the 2-year follow-up period.
Although switching anti-VEGF agents was offered to trial participants at the end of year 1 in T, it seems that only one patient chose to switch, which may mean that most patients felt they were doing well with the agent to which they were assigned. There are a number of reasons that a physician and a patient might choose one anti-VEGF agent over another (eg, cost, insurance coverage). Few eyes in any group lost substantial amounts of vision during 2 years of follow-up, so starting with any agent seems to be a choice that can be left to the discretion of the patient and their doctor without compromising visual outcome over a 2-year period in these patients who will need long-term treatment.
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