DRCR.net Protocol T: At 2 years, Eylea, Avastin, Lucentis all reduce need for injections, improve visual acuity

Two-year results of the Diabetic Retinopathy Clinical Research Network Protocol T study show that about half the number of anti-VEGF injections needed to treat diabetic macular edema in the first year of the study were needed in the second year, regardless of which study agent was used.

Perspective from Andrew P. Schachat, MD

The randomized clinical trial included 660 patients with visual acuity impairment from DME. Patients were randomized to receive intravitreal injections of 2 mg of Eylea (aflibercept, Regeneron), 1.25 mg of compounded Avastin (bevacizumab, Genentech) or 0.3 mg of Lucentis (ranibizumab, Genentech). Visual acuity improved in all three groups over the 2 years.

“This DRCR.net comparative effectiveness study for center-involved DME showed vision gains in all three drugs at the 2-year visit, with an average of almost half of the number of injections, slightly decreased frequency of visits and decreased amounts of focal/grid laser photocoagulation treatment in all three groups in the second year,” the study authors said.

Follow-up occurred every 4 weeks in the first year and every 4 weeks to 16 weeks in the second year, depending on the treatment course. Focal/grid laser photocoagulation was administered after 6 months if DME persisted.

At the 2-year follow-up, mean 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.

In patients with baseline visual acuity of 20/50 or worse, mean visual acuity improved by 18.1 letters in the aflibercept group, 13.3 letters in the bevacizumab group and 16.1 letters in the ranibizumab group.

In patients with baseline visual acuity of 20/32 to 20/40, mean visual acuity improved by 7.8 letters in the aflibercept group, 6.8 letters in the bevacizumab group and 8.6 letters in the ranibizumab group.

Focal/grid laser coagulation was administered in 41% of patients in the aflibercept group, 64% of patients in the bevacizumab group and 52% of patients in the ranibizumab group. – by Nhu Te

Disclosure: Wells reports he receives grants from Allergan, Ampio, KalVista, Emmes, Neurotech, Lpath, National Institutes of Health and Ophthotech; grants and non-financial support from Genentech and Regeneron, during the conduct of the study; grants, personal fees and non-financial support from Iconic; and grants and personal fees from PanOptica, outside the submitted work. Please see the full study for all other authors’ relevant financial disclosures.

Editor's note: Mean visual acuity was corrected from 18.3 letters to 18.1 letters in the aflibercept group due to a typographical error in the DRCR.net manuscript published in Ophthalmology.

Perspective

Andrew P. Schachat, MD

In the last few years, there has been a revolution in the management of diabetic macular edema, with anti-VEGF therapy being added to laser therapy. There has been FDA approval of ranibizumab and aflibercept to treat DME, and off-label bevacizumab is used as well. The DRCR.net group has taken the extremely important step of studying the comparative effectiveness of these three drugs for DME. The 1-year study results showed overall that the three drugs were similar, but for the pre-specified subgroups with worse vision at baseline or thicker maculas at baseline, aflibercept performed better. At the 2016 Macula Society meeting, the 2-year results were presented, and the manuscript was published online the same day in Ophthalmology.

The 2-year data show that fewer injections are needed in year 2. The median number of injections in year 2 was 5, 6 and 6 and over 2 years was 15, 16 and 15 in the aflibercept, bevacizumab and ranibizumab groups, respectively. Laser was needed in about half the eyes. And, the vision benefit was maintained: From baseline to 2 years, mean visual acuity letter score improved by 12.8 with aflibercept, 10 with bevacizumab and 12.3 with ranibizumab. For eyes with good vision at baseline, the three drugs behaved as they did in year 1 with no meaningful difference in outcomes. For eyes with poor vision at baseline, the outcomes showed a mean improvement of 18.1, 13.3 and 16.1 letters, respectively (aflibercept-bevacizumab: P = .020, aflibercept-ranibizumab: P = .18, ranibizumab-bevacizumab: P = .18). So, the advantage of aflibercept over ranibizumab noted at 1 year had decreased and was no longer statistically significant at 2 years, while aflibercept remained superior to bevacizumab. This is important information. But, for me, in part, the superiority of aflibercept is tempered by the cost. The 2-year data are now available, and it is our job to explain the outcomes and costs to patients. Patients with poor baseline vision and society will need to weigh the vision benefits at 2 years for the more costly drug.

Andrew P. Schachat, MD

Vice chairman, Cole Eye Institute, and professor of ophthalmology, Lerner College of Medicine

Disclosures: Schachat reports he is a full-time employee at the Cleveland Clinic, is a part-time employee at the state of Ohio, is a consultant for the American Academy of Ophthalmology and AnGes, receives royalties from Elsevier and is a stockholder for Easton Capital.

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Sources/Disclosures

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Source:

Wells JA, et al. Ophthalmology. 2016;doi:10.1016/j.ophtha.2016.02.022.