TREX-AMD trial finds visual gains from treat-and-extend vs. monthly

February 17, 2017

Treat-and-extend approach for neovascular AMD leads to beneficial results in 2-year clinical trial.

Take-home: Treat-and-extend approach for neovascular AMD leads to beneficial results in 2-year clinical trial.

Reviewed by Charles C. Wykoff, MD, PhD

A study using a treat-and-extend approach for wet age-related macular degeneration (AMD) found similar outcomes for both monthly and treat-and-extend patients over 2 years.

The goal of the treat-and-extend approach was to individualize ranibizumab (Lucentis, Genentech) dosing while optimizing visual benefits, said Dr. Wykoff, who is in private practice in Houston. This is in contrast to planned monthly doses of the anti-vascular endothelial growth factor (anti-VEGF) injections used in wet AMD patients.

“The goal is to maintain an exudation-free macula and avoid multiple disease recurrences as can occur with PRN dosing, while minimizing the treatment burden through fewer clinical visits, diagnostics, and treatments,” according to Dr. Wykoff’s presentation abstract.

The TREX-AMD-short for Treat and Extend Protocol in Patients with wet Age-Related Macular Degeneration-is a phase 3b multicenter trial that included 60 eyes that were not treated before and had a visual acuity of 20/32 to 20/500. Twenty eyes received monthly injections of ranibizumab, and 40 received treat-and-extend dosing.

Courtesy of Charles C Wykoff, MD, PhD

In the latter group, the eyes were treated every 4 weeks for a minimum of 3 injections until a dry macula was achieved. At that point, treatment was lengthened by 2-week intervals, until a maximum of 12 weeks.

“Once stability was achieved, the maximum extension interval was rechallenged, using a rigid prospective protocol,” Dr. Wykoff added.

Investigators used spectral domain optical coherence tomography (SD-OCT) to check for intraretinal and subretinal fluid and ophthalmoscopy to check for hemorrhage.

 

Study results

The mean patient age was 77 years, and the mean visual acuity was about 20/60 in both groups. Eighty-three percent of patients completed the trial’s full 2 years.

In the treat-and-extend group, 68% of patients achieved a dry macula. In the monthly group, patients gained a mean of 10.5 letters, compared with 8.7 letters in the treat-to-extend group. Both groups had similar results in terms of mean central macular thickness, Dr. Wykoff said.

At the 2-year time point, 37% of patients were prescribed an interval of 11 or 12 weeks in the treat-and-extend model, while one-third were receiving monthly dosing. The mean maximum tolerated extension interval was 8.5 weeks.

“Through 2 years, 20% of monthly and 30% of the treat-and-extend arm gained at least 15 letters,” Dr. Wykoff said.

While no monthly patients lost any letters, 13% of the treat-and-extend group lost at least 15 letters, a finding which Dr. Wykoff linked to progressive macular atrophy in 2 eyes. A closer look at the patients who lost letters showed that no patient lost vision due to exudative disease recurrence while the interval between treatments was extended.

Courtesy of Charles C Wykoff, MD, PhD

“One developed a retinal pigment epithelial tear following the first injection,” Dr. Wykoff said. “A second demonstrated progressive exudative disease activity despite monthly dosing, and 2 developed substantial macular atrophy with foveal involvement and visual acuity loss,”

From a safety perspective, the treat-and-extend group experienced 3 cases of progressive macular atrophy, compared with none in the monthly group.

Treat-and-extend offers the opportunity to individualize patient management and still achieve similar visual and anatomic gains, Dr. Wykoff concluded.

 

Charles C. Wykoff, MD, PhD

E: ccwmd@houstonretina.com

This article was adapted from a presentation Dr. Wykoff delivered at the 2016 Retina Subspecialty Day during 2016 American Academy of Ophthalmology annual meeting. Dr. Wykoff is a consultant for Allergan, Alimera Sciences, Bayer, Clearside Biomedical, DORC, Genentech, ONL Therapeutics, and Regeneron Pharmaceuticals. He is a speaker for Allergan and Regeneron.