Response to Anti-VEGF in Macular Edema Evident at 3 Months

Caroline Helwick

November 25, 2015

LAS VEGAS — For patients with diabetic macular edema, long-term response to vascular endothelial growth-factor (VEGF) inhibitors can be predicted after just three injections, according to a post hoc analysis of data from Protocol I of the Diabetic Retinopathy Clinical Research Network (DRCR.net).

Patients who did not respond to three monthly anti-VEGF injections were destined to remain relatively unresponsive at 3 years, said Pravin Dugel, MD, from the University of Southern California Keck School of Medicine in Los Angeles and Retinal Consultants of Arizona in Phoenix.

This is a group of patients who might benefit from treatments that have an alternate mode of action, he pointed out.

Dr Dugel presented results from the phase 3 Early Anti-VEGF Response and Long-term Efficacy (EARLY) study here at the American Academy of Ophthalmology 2015 Annual Meeting.

He and his colleagues evaluated 854 eyes from 691 patients with diabetic macular edema treated with ranibizumab according to an established protocol over a period of 3 years.

The team assessed study eyes for best corrected visual acuity after 3 months and throughout the study period. The results were striking; patients "tracked" according to their 12-week response.

In the group of patients who gained at least 10 letters after three injections, this strong response at 12 weeks was maintained during the 3-year study period. In the group of patients who gained five to nine letters, improvement was limited at 3 years. And in the group of patients who gained four letters or less, the benefit was minimal at 3 years, Dr Dugel reported.

"The point here is that three injections, after 12 weeks, can very confidently predict what's going to happen to the patient — not just for 1 year, but for up to 3 years," he told Medscape Medical News.

Table. Change in Mean Best Corrected Visual Acuity Over Time

Mean Letters Gained 0 to 4 Letter Group (n = 135) 5 to 9 Letter Group (n = 79) ≥10 Letter Group (n = 126)
At 3 months 0.3 6.9 15.2
At 1 year 2.8 8.2 16.5
At 3 years 3.0 8.2 13.8

 

After multivariate adjustment, there was a significant correlation in best corrected visual acuity gain for all three groups of patients between week 12 and years 1 and 3 (P < .001).

"The number gaining less than five letters was around 39%," Dr Dugel reported. "Overall, these patients do well on anti-VEGF agents, but when you look at the outcomes with more granularity, you see that many don't. Right now, this is the only way to predict who will be in that group."

 
All anti-VEGF agents are relatively similar in efficacy in this disease. There's no evidence for switching, and no evidence that switching from one anti-VEGF agent to another is better.
 

On the basis of these results, Dr Dugel said that clinicians might want to consider therapies with alternative modes of action for patients with diabetic macular edema who are inadequately responsive after three injections.

In fact, if a patient does not respond to an anti-VEGF agent after three injections, "consider alternative modes of therapy," he said.

But Dr Dugel said he would not switch to another anti-VEGF. "All anti-VEGF agents are relatively similar in efficacy in this disease. There's no evidence for switching, and no evidence that switching from one anti-VEGF agent to another is better," he explained.

A lack of response probably indicates a different disease mechanism at work, Dr Dugel reported.

Diabetic macular edema "may evolve from a condition that is primarily permeability-driven to one that is primarily inflammatory-driven, and in a new patient, you have no idea where they are on this spectrum. The patient may have thrown the multifactorial switch and may now be in the inflammatory phase as opposed to the early permeability phase of disease," he pointed out. "This is where steroids come in."

Dr Dugel said that the dexamethasone intravitreal implant (Ozurdex, Allergan) is the natural choice for the initial intervention. After that, there is fluocinolone acetonide (Iluvien, Alimera Sciences), which has also been approved by the US Food and Drug Administration.

This analysis of the EARLY data confirms what Ninel Gregori, MD, from the Bascom Palmer Eye Institute in Miami, has been doing for some time.

"By 3 months, I do think you know how a patient is going to do on anti-VEGF agents," she told Medscape Medical News. "This is how I have been managing patients already. What I do with my patients, in particular my diabetics, is to give 3 months of injections with bevacizumab, then evaluate. If they have improved, great, I continue the treatment. If they have not, I switch to a different anti-VEGF agent, usually aflibercept, and inject another three times. If there is still no change, I may go to a steroid next," she said.

Although this study was based on DRCR.net data, the analysis was not reviewed or approved by DRCR.net. Dr Dugel reports consulting for Allergan, Abbott Medical Optics, Acucela, Alcon Laboratories, Alimera Sciences, Digisight, Genentech, Novartis Pharmaceuticals, Ophthotech, Ora, Regeneron, and ThromboGenics. Dr Gregori has disclosed no relevant financial relationships.

American Academy of Ophthalmology (AAO) 2015 Annual Meeting. Presented November 14, 2015.

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