By Purnima S. Patel, MD
One-year results from the Diabetic Retinopathy Clinical Research Network’s (DRCR.net) comparative effectiveness study shows that aflibercept may be more effective than other anti-VEGFs in patients with diabetic macular edema, but only in those with worse baseline visual acuity.
The multicenter, randomized trial known as Protocol T evaluated the relative efficacy and safety of intravitreal aflibercept, bevacizumab and ranibizumab for center-involving diabetic macular edema, by clinical exam and on optical coherence tomography. Subjects included 660 patients with best-corrected visual acuities ranging from 20/32 to 20/320. Patients were followed every 4 weeks (± 1 week), with the primary outcome measure being mean change in visual acuity at 1 year.
Patients were randomized to receive aflibercept at a dose of 2.0 mg, bevacizumab at a dose of 1.25 mg (repackaged bevacizumab underwent sterility, purity, and potency testing) or ranibizumab at a dose of 0.3 mg. Patients receiving any anti-VEGF injections in the previous 12 months were excluded.
Improvement was defined as an increase in the visual-acuity letter score of 5 or more (approximately 1 Snellen line) or a decrease in the central subfield thickness of 10% or more. Worsening was defined as a decrease in the visual-acuity letter score of 5 or more or an increase in the central subfield thickness of 10% or more. Beginning at the 24-week visit – regardless of visual acuity and central subfield thickness – an injection was withheld if there was no improvement or worsening after two consecutive injections, but treatment was reinitiated if the visual acuity letter score or the central subfield thickness worsened. Laser photocoagulation (focal, grid or both) was initiated after 6 months for residual macular edema.
From baseline to 1 year, the mean visual-acuity letter score (range, 0 to 100 with higher scores indicating better visual acuity; 85 would be approximately 20/20) improved by 13.3 with aflibercept (p<0.001 vs. bevacizumab and p=0.03 vs. ranibizumab), by 9.7 with bevacizumab, and 11.2 with ranibizumab. Although the benefit was greater with aflibercept, the difference was driven by eyes with worse visual acuity at baseline.
- When initial visual acuity was between 20/32 and 20/40 (51% of participants), the mean improvement was 8.0 with aflibercept, 7.5 with bevacizumab, and 8.3 with ranibizumab (p>0.50 for each pairwise comparison).
- When initial visual acuity was 20/50 or worse, the mean improvement was greater for the aflibercept group (P <0.001 vs. bevacizumab, p=0.003 vs. ranibizumab) (18.9 aflibercept, 11.8 bevacizumab and 14.2 ranibizumab).
All three groups showed improvement in mean visual acuity by 4 weeks. In the eyes with visual acuity 20/50 or worse, the greater efficacy of aflibercept started to become apparent as early as 4 weeks after initiation of treatment.
Of a maximum of 13 injections, the aflibercept group had the fewest, with a median of 9 injections. The other two groups had a median of 10 injections. Laser photocoagulation was performed in 37% of aflibercept-treated eyes, 56% of bevacizumab-treated eyes, and 46% of ranibizumab-treated eyes (p<0.001 in overall comparisons).
- When looking only at the eyes with initial visual acuity ranging from 20/32 to 20/40, the median number of injections was 9 for each group, with 36% of aflibercept-treated eyes, 47% of bevacizumab-treated eyes, and 43% of ranibizumab-treated eyes receiving laser photocoagulation.
- When initial visual acuity was worse than 20/50, the median number of injections was 10 with aflibercept, 11 with bevacizumab, and 10 with ranibizumab with 37%, 65%, and 50%, respectively, receiving laser photocoagulation.
In summary, all patients with center-involving diabetic macular edema experienced improved vision whether receiving aflibercept, bevacizumab or ranibizumab, but the relative effect was dependent on baseline visual acuity. With good initial baseline visual acuity, no difference on average was seen between drugs. However, with initial visual acuities of 20/50 or worse, aflibercept was more effective in improving visual acuity.