Pegaptanib for neovascular age-related macular degeneration.
BACKGROUND
Pegaptanib, an anti-vascular endothelial growth factor therapy, was evaluated in the treatment of neovascular age-related macular degeneration.


METHODS
We conducted two concurrent, prospective, randomized, double-blind, multicenter, dose-ranging, controlled clinical trials using broad entry criteria. Intravitreous injection into one eye per patient of pegaptanib (at a dose of 0.3 mg, 1.0 mg, or 3.0 mg) or sham injections were administered every 6 weeks over a period of 48 weeks. The primary end point was the proportion of patients who had lost fewer than 15 letters of visual acuity at 54 weeks.


RESULTS
In the combined analysis of the primary end point (for a total of 1186 patients), efficacy was demonstrated, without a dose-response relationship, for all three doses of pegaptanib (P<0.001 for the comparison of 0.3 mg with sham injection; P<0.001 for the comparison of 1.0 mg with sham injection; and P=0.03 for the comparison of 3.0 mg with sham injection). In the group given pegaptanib at 0.3 mg, 70 percent of patients lost fewer than 15 letters of visual acuity, as compared with 55 percent among the controls (P<0.001). The risk of severe loss of visual acuity (loss of 30 letters or more) was reduced from 22 percent in the sham-injection group to 10 percent in the group receiving 0.3 mg of pegaptanib (P<0.001). More patients receiving pegaptanib (0.3 mg), as compared with sham injection, maintained their visual acuity or gained acuity (33 percent vs. 23 percent; P=0.003). As early as six weeks after beginning therapy with the study drug, and at all subsequent points, the mean visual acuity among patients receiving 0.3 mg of pegaptanib was better than in those receiving sham injections (P<0.002). Among the adverse events that occurred, endophthalmitis (in 1.3 percent of patients), traumatic injury to the lens (in 0.7 percent), and retinal detachment (in 0.6 percent) were the most serious and required vigilance. These events were associated with a severe loss of visual acuity in 0.1 percent of patients.


CONCLUSIONS
Pegaptanib appears to be an effective therapy for neovascular age-related macular degeneration. Its long-term safety is not known.
Gragoudas
Evangelos S
ES
Retina Service, Massachusetts Eye and Ear Infirmary and Harvard Medical School, 243 Charles St., Boston, MA 02114, USA. evangelos_gragoudas@meei.harvard.edu
Adamis
Anthony P
AP
Cunningham
Emmett T
ET
Feinsod
Matthew
M
Guyer
David R
DR
D000368:Aged; D000369:Aged, 80 and over; D052157:Aptamers, Nucleotide; D020256:Choroidal Neovascularization / Q000000981:diagnostic imaging / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007267:Injections / Q000009:adverse effects; D008268:Macular Degeneration / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009841:Oligonucleotides / Q000494:pharmacology / Q000627:therapeutic use*; D010778:Photochemotherapy; D011446:Prospective Studies; D011859:Radiography; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D014792:Visual Acuity / Q000187:drug effects; D014822:Vitreous Body
D052157:Aptamers, Nucleotide; D009841:Oligonucleotides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C495058:pegaptanib