October 2014

 

RETINA

 

New insights from the VIEW studies of aflibercept for AMD


by Tony Realini, MD, MPH

 
   
Intravitreal injection

Intravitreal injection into the pars plana Source: Karl Brasse, MD, EyeLand Design

The development of inhibitors to vascular endothelial growth factor (VEGF) has forever altered the therapeutic landscape for a host of retinal vascular disorders including age-related macular degeneration (AMD), as well as macular edema attributable to diabetes or retinal vein occlusion. These agents have the power to prevent vision loss and, in many cases, improve vision by reducing macular fluid. In clinical trials, more than 9 out of 10 patients remained stable during active treatment with the various agents, and approximately 3 in 10 saw visual acuity gains of 3 lines or more.

Clinical trials are necessarily limited in duration, while AMD is a lifelong disease. Also, clinical trials typically enroll only 1 eye, while AMD is almost always bilateral. These aspects of clinical trial design can leave unanswered key questions that patients want answered: What will happen to me over the long term? Will I lose vision in my other eye? Post hoc analysis of the aflibercept VIEW study data has provided insight into these important clinical questions.

Long-term outcomes

The 1-year outcomes of the combined VIEW 1 and VIEW 2 phase 3 studies of aflibercept for neovascular AMD have been previously published.

These studies compared monthly dosing and every other month dosingafter 3 initial monthly dosesof intravitreal aflibercept with monthly ranibizumab, said Jean-Franois Korobelnik, MD, University of Bordeaux, France. After 52 weeks, all treatment arms had similar visual, morphologic, and safety outcomes. These results were consistent through a total of 96 weeks as well. But what about long-term outcomes? A subset of 323 patients from the VIEW 1 study were followed for up to an additional 112 weeks to further evaluate long-term safety and efficacy in patients with neovascular AMD, said Dennis Marcus, MD, Augusta, Ga. These patients were enrolled in an open label rollover study, and during the extended follow-up, all patients were seen at least every 12 weeks. At each quarterly visit, patients received 2 mg aflibercept injections and could receive them as frequently as monthly if necessary. Following FDA approval of intravitreal aflibercept, the protocol was amended in June 2012 to require dosing every 8 weeks. Over an average follow-up of 112 weeks beyond the 96-week primary study endpoint, patients received an average of 12.9 additional intravitreal injections. In the primary VIEW study, the mean visual acuity gains of this cohort were +10.5 letters and +10.2 letters, respectively, at 52 and 96 weeks. By 208 weeks, the average visual acuity gain from baseline was +6.8 letters.

The visual acuity gains achieved by treatment with anti- VEGF therapy in VIEW 1 were largely maintained with continued treatment with intravitreal aflibercept 2 mg over a period of greater than 2 years, said Dr. Marcus.

The 3- to 4-letter loss of acuity occurred gradually over time, suggesting that either the underlying disease worsened under treatment or possibly that treatment becomes less effective over time. A third possibility is that quarterly evaluation and treatment may not be an adequate care process for neovascular AMD during the maintenance phase of therapy.

The fellow eye

AMD is almost always a bilateral disease, even though there may be asymmetry of both onset and severity. If both eyes met eligibility criteria for the VIEW studies, the eye with the worse visual acuity was enrolled. If both eyes had active wet AMD, the untreated eye was the better eye. What happens to these fellow eyes over time? Dr. Korobelnik and colleagues have begun the process of evaluating this issue in a post hoc analysis of the combined VIEW 1 and 2 data sets comprising 2,412 patients. They recently described the baseline characteristics of these eyes as a first step to assessing change over time.

As expected, visual acuity in fellow eyes was better than in study eyes by just over 11 ETDRS letters. Overall, two-thirds of fellow eyes had acuity of 66 letters or more, compared to just 20% of study eyes.

The majority of fellow eyes had signs of AMD at baseline, said Dr. Korobelnik. A full 90% had hard and/or soft drusen, and 88% had pigment changes in the subfoveal or extrafoveal regions. Also, 35% of fellow eyes had clinical signs of prior choroidal neovascularization at baseline, he said.

Practical implications

AMD is a lifelong disease. As the long-term extension of the VIEW 1 study demonstrates, there is slow but steady attrition of visual acuity over time even in eyes treated with a proven effective therapy. Tools to assess the risk of blindness from AMD have not been developed or validated. However, this long-term observation may assist physicians in counseling the patients who inevitably ask, Doctor, will I go blind from this disease? As for the fellow eye, observations from long-term studies may shed better light on the natural history of AMD and visual prognosis. Ongoing analyses will evaluate the development of new choroidal neovascularization in the fellow eyes among patients in the VIEW studies, Dr. Korobelnik said.

Editors note: Dr. Korobelnik has financial interests with Alcon (Fort Worth, Texas), Allergan (Irvine, Calif.), Bayer (Leverkusen, Germany), Novartis (Basel, Switzerland), Roche (Basel, Switzerland), Thea (Clermont-Ferrand, France), and Carl Zeiss Meditec (Jena, Germany). Dr. Marcus has financial interests with Acucela (Seattle), Alcon, Allergan, Genentech (South San Francisco), GlaxoSmithKline (Brentford, U.K.), Ophthotech (New York), Pfizer (New York), Regeneron (Tarrytown, N.Y.), and ThromboGenics (Leuven, Belgium).

Contact information

Korobelnik
: jean-francois.korobelnik@chu-bordeaux.fr
Marcus: dmarcus@southeastretina.com

New insights from the VIEW studies of aflibercept for AMD New insights from the VIEW studies of aflibercept for AMD
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