Year-2 Protocol T data paints different scenario from year-1
Planned subgroup analysis
But the comparison has “limited utility” because of the close correlation to baseline vision, he said. For Protocol T, the DRCR.net had predetermined to stratify outcomes into “better baseline vision”—those with 20/32 to 20/40 on the Early Treatment of Diabetic Retinopathy Study chart—and worse baseline vision, people with 20/50 or worse on the ETDRS chart.
At year 2, the better baseline vision group sustained their initial gains of about 8 letters,” Dr. Wells said. “An area-under-the-curve (AUC) analysis of this better baseline vision subgroup also confirmed that there were no differences between the 3 arms at the 2-year endpoint.”
However, at 2 years in the worse baseline group, “the difference between aflibercept and ranibizumab had disappeared and was no longer significant, whereas aflibercept remains superior to bevacizumab,” Dr. Wells said, adding the AUC analysis found the average daily change in vision was greater for aflibercept over 2 years than the other 2 agents.
Vision & anatomic outcomes
By Year 2, “about 50% to 60% of eyes gained 3 or more lines of vision, which calls into question the clinical relevance of the difference in the treatments at the 2-year endpoint. However, a mean AUC analysis of eyes gaining 3 or more lines over 2 years showed some superiority of aflibercept,” Dr. Wells said.
Anatomically, bevacizumab reduces the edema less effectively than the other two agents, he pointed out. Continuing with the split between the better baseline and worse baseline groups, Dr. Wells said the reduction was almost 50% less with bevacizumab than with the other 2 agents at years 1 and 2 in eyes with better baseline vision. But in the eyes with worse baseline vision, bevacizumab was inferior only to aflibercept at Year 2.
“Eyes treated with bevacizumab were less likely to achieve the normal OCT central subfield thickness of less than 250 µm in both the better baseline vision subgroup and in the worst baseline vision subgroup,” he said.
Focal grid laser during the course of the study had little effect, Dr. Wells added.
“When we looked at the effect on OCT thickness over the course of the 2 years, in the better baseline vision subgroup eyes that received no focal laser at all during showed no additional reduction in OCT thickness in the second year,” Dr. Wells explained. “Similarly, though, eyes that received laser between 6 months and 2 years in this better baseline vision subgroup also showed no additional reduction in OCT thickness in the second year.”
In the worse baseline vision subgroup, eyes that never received the laser showed no additional reduction in OCT thickness in the second year. If the eyes had undergone laser, though, those in the bevacizumab arm showed additional reductions in OCT edema in Year 2.
Safety outcomes were similar across all three groups during Years 1 and 2, with the exception of pre-specified Antiplatelet Trialists’ Collaboration (APTC) adverse events, where 12% of the patients in the ranibizumab group experienced an event compared to 5% and 8% in the aflibercept and bevacizumab groups, respectively.