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Follow-up to ANCHOR, MARINA, HORIZON trials shows mixed long-term results
Letter scores were stable or improved from baseline in 43% of eyes but decreased by 15 letters or more in 34%.
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About one-third of patients from the ANCHOR, MARINA and HORIZON trials had good visual acuity and about one-third had poor vision after approximately 7 years, a study found.
Results of the SEVEN-UP study showed that patients with exudative age-related macular degeneration who were treated with intravitreal Lucentis (ranibizumab, Genentech) were still at risk for significant long-term vision loss.
The authors assessed long-term outcomes 7 to 8 years after initiation of ranibizumab in the ANCHOR, MARINA and HORIZON trials, pivotal phase 3 clinical trials designed to gauge the safety and efficacy of intravitreal ranibizumab for exudative AMD. HORIZON, an open-label extension trial, included patients who had participated in ANCHOR and MARINA.
Aside from the major clinical trials, there are scant data on the long-term safety and efficacy of ranibizumab, the authors said.
“Almost all of the high-level clinical trial data that we have on treatment and therapies for macular degeneration are limited to 1-year or 2-year results. So, the goal here is to look at the longest possible results that you can obtain,” Robert B. Bhisitkul, MD, PhD, the corresponding author, said in an interview with Ocular Surgery News.
The study was published in Ophthalmology.
Patients and methods
The SEVEN-UP study included 65 patients who participated in the ANCHOR, MARINA and HORIZON trials. Participants were recruited at 14 centers to undergo a return evaluation, with a mean age at this point of approximately 82 years.
The primary outcome measure was the percentage of patients with best corrected visual acuity of 20/70 or better. Secondary measures were mean change in letter scores and anatomic findings on fluorescein angiography, spectral-domain optical coherence tomography and fundus autofluorescence.
Mean follow-up was 7.3 years after entering the ANCHOR or MARINA trials and 3.4 years after exiting the HORIZON trial.
Bhisitkul said that after the clinical trials, patients received other drugs such as Avastin (bevacizumab, Genentech) and were treated less frequently than during the trials.
“Instead of them being treated every month the way they were when they were in the clinical trial, they were treated more like less than two times a year. So, given all of those caveats, it was a difficult study to re-enact,” he said. “The best way to do this study would be to start today and go out for the next 7 years with a clinical trial of monthly Lucentis or whatever you want to use for macular degeneration.”
Results and observations
At a mean 7.3 years after entry into the ANCHOR or MARINA trials, BCVA was 20/70 or better in 37% of eyes and 20/40 or better in 23%. BCVA was 20/200 or worse in 37% of eyes.
Letter scores were stable or improved compared with ANCHOR and MARINA baseline values in 43% of eyes. Scores improved by 15 letters or more in 12% of eyes but decreased by 15 letters or more in 34% of eyes.
The mean decline in letter scores from baseline was 8.6 letters (P < .005).
“Overall, when you pool all of the population together, there was a mean loss of about eight letters since the initial beginning of the trial,” Bhisitkul said. “So, that initial increase that we were all so excited about seeing, eight to nine letters, occurred when they were getting monthly injections, but now, 7 years later, when they’ve been on much lower-frequency treatment and different types of treatment, overall they’re below where they started at baseline.”
In retrospect, the vision loss can be attributed mainly to undertreatment, Bhisitkul said.
“I don’t think there’s any getting around that a major factor was undertreatment,” he said. “As a whole, most of us started treating our patients in those years with very low frequency, and by now, we would consider this undertreatment. At the time, we didn’t recognize it as such.”
Patients who participated in the SEVEN-UP study received a mean 6.8 ranibizumab injections for a mean interval of 3.4 years after the study. Patients who received 11 or more injections after the SEVEN-UP trial gained significantly more letters than other patients (P < .05).
No further follow-up study of ANCHOR, MARINA and HORIZON patients is planned, Bhisitkul said.
“It was hard enough to put this one in place. As far as plans to do so, nothing is currently in place, although a wish list for me would be to do the Ten-Up study and see them 10 years after the initiation,” Bhisitkul said. – by Matt Hasson