Regular VEGF Inhibitor Dosing Better in Macular Degeneration

Neil Osterweil

April 18, 2014

TOKYO — To preserve visual acuity in patients with neovascular age-related macular degeneration, staying the course appears to be a better strategy than reactive as-needed treatment, according to 2 parallel clinical trials.

Patients maintained on a stable proactive regimen of quarterly intravitreal injections with the vascular endothelial growth-factor (VEGF) inhibitor aflibercept (Eylea, Regeneron) had more stable visual outcomes than patients treated on a reactive basis. This finding comes from a post hoc analysis of anatomic and functional outcomes in the second year of the Vascular Endothelial Growth Factor Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration (VIEW) studies.

"Switching from an exclusively proactive treatment scheme to a scheme with a reactive component leads to a significant loss of visual acuity in a subgroup of our patients," said investigator Gisbert Richard, MD, director of the University Eye Hospital Hamburg-Eppendorf in Germany.

"Lost vision is not regained after retreatment with a reactive injection, despite visual acuity gains up to week 52 under a proactive treatment schedule," he added.

An analysis of data from VIEW1 and VIEW2 was presented here at the World Ophthalmology Congress 2014.

The VIEW studies were randomized phase 3, multicenter, double-masked, active-controlled studies of patients with neovascular age-related macular degeneration. VIEW1 was conducted in Canada and the United States, and VIEW2 was conducted in Asia, Australia, Europe, and South America.

The 2412 VIEW patients were randomized to receive 1 of 4 treatments for 52 weeks: aflibercept 2.0 mg every 8 weeks after 3 initial monthly doses; aflibercept 2.0 mg every 4 weeks; aflibercept 0.5 mg every 4 weeks; or ranibizumab (Lucentis, Genentech) 0.5 mg every 4 weeks.

In both VIEW studies, the proportion of patients meeting the primary efficacy end point — loss of fewer than 15 letters of visual acuity from baseline to week 52 — was comparable in the 2.0 mg aflibercept groups and the ranibizumab group.

From weeks 52 to 96, patients in all 4 groups received a minimum of 3 injections of aflibercept 2.0 mg at 12-week intervals. Patients who met the following prespecified criteria could be treated more frequently: new or persistent fluid on optical coherence tomography, increase in central retinal thickness of at least 100 µm over the lowest previous value, loss of at least 5 ETDRS letters from the best previous score in conjunction with recurrent fluid, new-onset classic neovascularization, new or persistent leak on fluorescein angiography, or new macular hemorrhage.

In their analysis, Dr. Richard and colleagues compared best corrected visual acuity in patients maintained on regular doses of a VEGF inhibitor and those treated on an as-needed basis.

All groups showed a slight trend toward mean visual loss in the second year.

Roughly half of all patients in each group received the minimum number of mandatory quarterly injections; in these patients, best corrected visual acuity was maintained out to week 96.

There was, however, a subgroup of about 20% of all patients who lost at least 5 EDTRS letters from week 52 to week 96 when treated with a reactive dosing approach, despite receiving 4 or 5 injections of aflibercept.

"This was not paralleled or preceded by changes in central retinal thickness," Dr. Richard reported.

The investigators assessed patients who lost at least 5 letters between 2 consecutive visits from week 52 to week 64 who received an injection at the second visit. These patients had stable vision after the second visit, but did not regain the vision they had had at week 52.

"Proactive, quarterly treatment in year 2 was sufficient to maintain visuals gains from year 1 in approximately 40% to 50% of patients. Overall, visual acuity is generally maintained in year 2. However, a slight trend in loss of vision suggests that a proactive treatment schedule results in more stable outcomes with intravitreal aflibercept or ranibizumab," Dr. Richard explained.

Evidence to date suggests that an as-needed strategy is not sufficient to maintain visual acuity in some patients, said Paul Mitchell, MD, professor of clinical ophthalmology and eye health at the University of Sydney in Australia, who was not involved in the post hoc analysis.

"It looks like there is a general move toward a different regimen than PRN," he told Medscape Medical News. "With PRN, we're starting to lose some vision in the longer term in some patients, so extended treatment seems to be an alternative approach that people are moving to. There's a suggestion that it might be better, but it has not yet been examined in large clinical trials," said Dr. Mitchell.

The study was supported by Regeneron. Dr. Richard is a consultant for Bayer Healthcare. Dr. Mitchell reports receiving consultancy fees, lecture fees, and travel support from Novartis Pharma AG, Pfizer, Solvay (Abbott), Bayer, Alcon, and Allergan.

World Ophthalmology Congress (WOC) 2014: Abstract FP-FR-17-7. Presented April 4, 2014.

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