In an evaluation of the anatomic changes of CNV lesions, patients treated with ranibizumab (Lucentis, Genentech) in the PIER study had smaller changes than patients who had received sham injections.
Palm Beach Gardens, FL-The angiographic results of the PIER study indicate that at 24 months the ranibizumab dosing regimen (Lucentis, Genentech) resulted in smaller changes in the area of choroidal neovascularization (CNV) versus sham injection, according to Mark Michels, MD, a retina specialist in private practice in Palm Beach Gardens, FL.
"The beneficial effect of ranibizumab on key anatomic outcomes at month 12 was maintained at month 24 for total area of CNV, total area of the lesion, and area of classic CNV," Dr. Michels said. "Within treatment groups, change from baseline in the key anatomic outcomes at 12 months did not significantly differ in patients who lost <15 letters compared with those who lost ≥15 letters at month 24."
PIER is the acronym for a phase IIIb, multicenter, randomized, double-masked, sham injection-controlled study of the efficacy and safety of ranibizumab in subjects with subfoveal choroidal neovascularization with or without classic CNV secondary to age-related macular degeneration.
The study was initiated in September 2004 and completed in March 2007. At the start of the study, all patients randomly assigned to the sham arm were assigned to receive sham injections following the same schedule as those subjects who received the drug. All control subjects remaining in the study at the time of a crossover amendment, in February 2006, were offered the option of receiving ranibizumab 0.5 mg on a quarterly basis after completing their 12-month visit.
"The crossover amendment was prompted by a review of the 12-month data from the two pivotal phase III trials, MARINA and ANCHOR, but treatment schema were put in place to maintain masking of the original treatment assignment," Dr. Michels said. "Then, later in the year, all subjects remaining in the study by the rollover amendment were offered the option of receiving 0.5 mg ranibizumab dosing monthly for the remainder of the study. The rollover amendment was prompted by a review of the 12-month PIER data as well as further analysis of the MARINA and ANCHOR data."
The primary endpoint in the PIER study was the mean change from baseline at 12 months in best-corrected visual acuity score. Key anatomic endpoints included the mean change from baseline in the total area of CNV at 12 and 24 months and the mean change from baseline in total area of leakage from CNV at 12 and 24 months. Exploratory endpoints included change from baseline in the area of classic CNV in patients with a classic component at 12 and 24 months and mean change from baseline in the total area of the lesion at the same timepoints.
The study enrolled 184 subjects; the three arms were evenly matched, and the lesion sizes were considered relatively small. Fundus photography and fluorescein angiography were performed at baseline and at months 3, 5, 8, 12, and 24. The University of Wisconsin Fundus Photography Reading Center retrospectively reviewed the images.
Mean change from baseline
Summarizing the results, Dr. Michels first turned to the mean change from baseline in the areas of classic CNV, which are areas of well-demarcated hyperfluorescence appearing early in the angiography and showing early and progressive fluorescein leakage.
"The PIER ranibizumab dosing regimen resulted in a mean decrease from baseline compared with increases from baseline with sham injection in area of classic CNV at both month 12 and month 24," he said. "Because month 24 was the only timepoint captured after month 12, the straight line (on his slides) connecting month 12 and 24 results should not be interpreted as implying a gradual change, because the change could have been of a different functional form."
The mean change from baseline in total area of CNV at month 24 was 0.29 disc areas (DA) for the 0.3-mg arm, 0.64 for the 0.5-mg arm, and 1.90 for the sham arm (p < 0.003). At month 12, the respective changes from baseline were 0.18, 0.43, and 2.08 DA (p < 0.002). The definition for this parameter included classic and atypical classic CNV, fibrovascular pigment epithelial detachment (PED), occult neovascularization, and late leakage of undetermined source.
"Here again, the PIER ranibizumab dosing regimen resulted in smaller increases from baseline in total area of CNV compared with sham injection at months 12 and 24," Dr. Michels said.
He and fellow investigators also measured mean change from baseline in the total area of lesion, which included not only CNV but other abnormalities considered likely to obscure underlying CNV. Examples include contiguous blocked fluorescence, contiguous thick blood, serous PED, and noniatrogenic subretinal fibrous tissue and atrophic scars.
As expected, the PIER ranibizumab dosing regimen resulted in a smaller increase from baseline in total area of the lesion compared with sham at months 12 and 24, Dr. Michels said.