5-year CATT analysis finds anti-VEGF drugs a long-term AMD therapy

June 23, 2017

After 5 years of follow-up in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT), the visual acuity gains achieved during the first 2 years of anti-VEGF treatment were not maintained, the choroidal neovascular lesions continued to evolve with evidence of persistent activity in some eyes, and there was increased retinal thinning and geographic atrophy (GA).

After 5 years of follow-up in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT), the visual acuity gains achieved during the first 2 years of anti-VEGF treatment were not maintained, the choroidal neovascular lesions continued to evolve with evidence of persistent activity in some eyes, and there was increased retinal thinning and geographic atrophy (GA). 

The take-home message, nevertheless, is that 50% of the patients had 20/40 or better visual acuity at 5 years after enrollment.

“That visual acuity outcome would have been unimaginable in the era prior to anti-VEGF therapy,” said Daniel F. Martin, MD, CATT Study chairman and chairman, Cole Eye Institute, Cleveland Clinic, Cleveland, OH.

CATT randomly assigned patients with active AMD-related choroidal neovascularization (CNV) to 1 of 4 treatment groups to receive bevacizumab (Avastin, Genentech) or ranibizumab (Lucentis, Genentech) given monthly or as needed (PRN). At 1 year, patients assigned to the monthly treatment groups were re-randomized to monthly or PRN treatment.

 

Majority in follow-up study

Planned duration of CATT was 2 years, and the study ended in December 2011. In 2014, the National Eye Institute funded a follow-up study in which the 1,117 patients alive at the end of CATT were asked to return for a follow-up visit for evaluations that would include best corrected ETDRS visual acuity, color fundus photographs, fluorescein angiography (FA), and spectral domain optical coherence tomography. Patient records were also reviewed to determine anti-VEGF treatment since CATT ended as well as adverse events.

A total of 647 of the eligible patients (71%) participated in the follow-up study. They had a mean age of 83 years. Mean duration of follow-up since randomization was 5.5 years with a range of 4.3 to 7.1 years.

“A lot of people have asked if we are able to do a 10-year follow-up. Given the age of our patients, 5 years is probably the longest follow-up you will see from this study,” said Dr. Martin.

Most patients were receiving ongoing care for their AMD, although the mean number of visits per year declined from years 3 through 5 from 8 to 7 to 6 visits. The vast majority of patients (91%) received continued care at a CATT center, and the majority of patients (60%) were treated with one or more drugs differing from their CATT-assigned treatment. Almost no patient continued planned monthly treatment.

“For that reason, the goal of the CATT follow-up study was not to look at differences between drugs or dosing regimens,” Dr. Martin said. “The goal was to assess the global effects of any anti-VEGF therapy on visual acuity and anatomical outcomes after 5 years.” 

Visual acuity analysis

The analyses of visual acuity data showed an average loss of 11 letters from the level achieved at the end of CATT, which represented an average loss of 3 letters from mean baseline vision. Mean loss from the end of year 2 to year 5 was less in the patients originally assigned to bevacizumab compared with those originally assigned to ranibizumab (-9 versus -13 letters), and the between-group difference was statistically significant. Dr. Martin pointed out, however, that he did not consider the difference meaningful.

Data on injection frequency reinforced knowledge that there is a continued injection burden when treating AMD. The mean number of injections administered per patient in years 3, 4, and 5 after CATT entry was 5, 5, and 4, respectively.

 
“The distribution, however, is very wide,” said Dr. Martin. “Fifteen percent of patients did not require any additional treatment, which is a decent number. And, it is fascinating that most of this subgroup did not need treatment after 1 year.”

“It is probably true that undertreatment may be a bigger problem than overtreatment, but I can’t say that definitively from our data,” he added,

Citing data showing that the distribution of visual acuity in patients, who did not receive any additional treatment after year 2, was almost the same as in the entire cohort, Dr. Martin said poor vision does not appear to explain why patients are not receiving ongoing treatment.  

Anatomical results

The anatomical results showed that 83% of patients had residual fluid at 5 years of follow-up, and it was mostly intraretinal fluid. There was persistent leakage on (FA) in 25% of eyes.

Mean total foveal thickness remained almost unchanged from the end of year 2 to the end of year 5 (298 µm versus 278 µm). Atrophy in the retina and in the retinal pigment epithelium and choriocapillaris, however, increased.

The proportion of patients with an abnormally thin retina (i.e., <120 µm thickness) increased from 22% at the end of year 2 to 36% at the end of year 5. From the end of year 2 to the end of year 5, the proportion of patients with foveal and nonfoveal GA doubled from 20% to 41%, and total CNV lesion area grew by 50% from 8 to 13 mm2 over the 3 years after CATT ended. 

Daniel F. Martin, MD

P: (216) 444-0430

E: martind@ccf.org

This article is based on a presentation Dr. Martin delivered at the 2016 Retina Subspecialty Day, prior to the 2016 American Academy of Ophthalmology meeting. A paper reporting the results was published prior to the meeting [Ophthalmology. 2016;123(8):1751-1761]. Dr. Martin has no relevant financial interests to disclose.