Update on results of trial for age-related macular degeneration

March 1, 2010

The combinations of verteporfin photodynamic therapy (PDT), ranibizumab, and dexamethasone and verteporfin PDT and ranibizumab for treating patients with choroidal neovascularization secondary to age-related macular degeneration resulted in fewere re-treatments compared with ranibizumab alone in the phase II exploratory RADICAL study, according to one investigator.

Philadelphia-The combinations of verteporfin photodynamic therapy (PDT) (Visudyne, QLT Inc./Novartis), ranibizumab (Lucentis, Genentech), and dexamethasone and verteporfin PDT and ranibizumab for treating patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) resulted in fewer re-treatments compared with ranibizumab alone in the phase II exploratory RADICAL Study, according to Allen C. Ho, MD.

"The purpose of the study was to determine if combination therapy reduces re-treatment rates compared with ranibizumab monotherapy while maintaining similar visual results and an acceptable safety profile," said Dr. Ho, professor of ophthalmology, Thomas Jefferson University, and attending surgeon, Retina Service, Wills Eye Hospital, Philadelphia.

Treatment groups

All 162 patients (162 eyes) had subfoveal CNV due to AMD and visual acuity (VA) levels between 20/40 and 20/320. The patients were randomly assigned to one of the four treatment groups.

In the monotherapy group, the patients were treated at baseline and months 1 and 2 and then followed monthly for 1 year. In the triple- and double-therapy groups, the patients were treated at baseline and then monitored each month for 1 year.

"Re-treatment criteria were strict and included optical coherence tomography (OCT) and fluorescein angiography," Dr. Ho said. "If the central retinal thickness exceeded 250 μm or 50 μm more thickening compared with the best previous OCT results, re-treatment was performed."

If those criteria were not present but leakage was seen on fluorescein angiography then re-treatment was performed.

Results showed that all groups had initial and sustained increases in VA throughout the study. There was no evidence of superiority or inferiority of any of the four treatments groups since sample sizes were small and confidence intervals were wide. Patients who gained three lines of VA ranged from 24% to 31% in all groups at the 1-year follow-up visit, with no significant differences among the groups; from 7% to 10% of patients in all groups lost three lines or fewer.

Primary endpoint

The cumulative number of re-treatments based on OCT or fluorescein angiography was the primary endpoint of this study. The results showed that in the monotherapy group, the average number of treatments was 5.4 over the 1-year study (including two treatments beyond baseline mandated by the monotherapy study protocol). The patients in the combination therapy groups received fewer re-treatments. The patients in the half-fluence triple-therapy group had the fewest number of re-treatments, with an average of 3. The patients in the quarter-fluence triple-therapy group and the half-fluence double-therapy group each received an average of 4 re-treatments, Dr. Ho said.

"The re-treatment rates differed between OCT and fluorescein angiography [criteria]," he said. "The OCT re-treatment rates for ranibizumab monotherapy were higher compared with the combination therapies. With fluorescein angiography, the re-treatment rates were comparable among the four treatment groups."

There were no new safety issues observed regarding PDT, dexamethasone, or ranibizumab injection therapy; no patients developed endophthalmitis.

The IOP was elevated temporarily in 10% of patients and this resolved with medical treatment.

"The combination therapy at 1 year demonstrated no safety concerns with reduced fluence treatment compared with monotherapy," he said. "Fewer re-treatments were needed with combination therapy compared with the monotherapy group. VA levels were similar across all groups although definitive conclusions can not be drawn from this phase II exploratory study.

"Combination therapy may be considered for patients with exudative AMD who find it difficult to return for frequent re-treatment visits," Dr. Ho concluded.

FYIAllen C. Ho, MD
E-mail: acho@att.net

Dr. Ho is a consultant for QLT Inc.