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The Verteporfin Intravitreal Triamcinolone Acetonide Study (VERITAS) of intravitreal triamcinolone acetonide (Kenalog, Bristol-Myers Squibb) or pegaptanib (Macugen, Pfizer) in combination with photodynamic therapy (PDT) with verteporfin (Visudyne, Novartis Pharmaceuticals) was underpowered to reach definitive conclusions about the therapies.
New Orleans-The prospects for successful combination therapies to treat age-related macular degeneration (AMD) are an intriguing avenue for research. Speaking at the American Academy of Ophthalmology annual meeting, Peter K. Kaiser, MD, reported the 12-month results of the Verteporfin Intravitreal Triamcinolone Acetonide Study (VERITAS), which was carried out to evaluate the safety and efficacy of intravitreal triamcinolone acetonide (Kenalog, Bristol-Myers Squibb) or pegaptanib (Macugen, OSI/Eyetech/Pfizer) in combination with photodynamic therapy (PDT) with verteporfin (Visudyne, Novartis Pharmaceuticals).
"The rationale for VERITAS with different mechanisms of action of a combination of treatments is that the therapy causes occlusion of the choroidal neovascularization (CNV), but this causes up-regulation of vascular endothelial growth factor (VEGF) and inflammatory mediators," said Dr. Kaiser, director, Digital OCT Reading Center, Cole Eye Institute, Cleveland Clinic, Cleveland, and chairman of VERITAS. "Adding an angiogenic drug or steroid might block this effect and provide better outcomes."
The primary outcome of the study was the percentage of patients who lost fewer than 15 letters of visual acuity (VA) by the 12-month time point.
Patients were included in the trial if they were aged more than 50 years and had any type of subfoveal CNV as the result of AMD. When the lesion was occult without classic CNV, evidence of recent progression of the disease had to be present. The CNV had to make up more than 50% of the lesion, which had to be smaller than 5,400 μm at its greatest linear dimension.
The baseline VAs had to range between 20/40 and 20/320.
Patients were excluded if they had undergone a previous subfoveal treatment.
The patients were randomly assigned 1:1:1 to standard fluence PDT and pegaptanib or 1 mg or 4 mg of triamcinolone.
A total of 111 patients were enrolled when the study was finished early; this number was less than the original 339 patients desired because of the results of the study of ranibizumab (Lucentis, Genentech), Dr. Kaiser explained. The number of patients reduced the power of the study from 80% to 43%, he added.
At baseline, the three groups received the combination treatments. Pegaptanib was administered every 6 weeks; if leakage was seen on fluorescein angiography at 3-month intervals, then standard fluence PDT was administered.
At 6-week intervals, the other two groups received sham injections; at 3-month intervals, if leakage was visible on fluorescein angiography, then the combination therapy was repeated.
Besides the reduced study power, Dr. Kaiser also pointed out another limitation, i.e., that the study was halted early and, therefore, the baseline characteristics were unbalanced. In the group that received pegaptanib, significantly worse VA was seen compared with the group treated with 1 mg of triamcinolone.
In addition, both groups treated with triamcinolone had a significantly greater number of patients with cataract.
The lesion types also were unbalanced among the treatment groups, with more classic CNV in the group treated with pegaptanib and more occult CNV without a classic component in the group treated with 4 mg of triamcinolone, Dr. Kaiser said.
Regarding the primary endpoint of loss of fewer than 15 letters of vision at the 12-month time point, no significant difference was seen among the treatment groups.
"In all groups, the mean change in VA from baseline lost a mean decrease in vision and there was no difference among the treatment groups," he reported. "In the PDT plus pegaptanib group, there was a gain of more than 3 lines of vision in 13.2% of patients; there was no gain in the 4-mg triamcinolone group."
An almost-significant difference was seen in the anatomic results between the 4-mg triamcinolone group and the pegaptanib group in terms of the CNV size and the CNV leakage, Dr. Kaiser said.
Optical coherence tomography (OCT) images showed that all treatment groups had a "dramatic reduction" in retinal thickness by the first examination at 3 months, he said, adding that this improvement was sustained at 12 months.
"Anatomically, the patients did very well," Dr. Kaiser stated.