Pegaptanib and Age-Related Macular Degeneration
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Gragoudas and coworkers (Dec. 30 issue)1 report that in a trial of pegaptanib in patients with exudative macular degeneration, patients treated with intravitreal injections of 0.3 mg of active substance had less functional deterioration than did the controls, who received sham injections. It is not clear why the highest concentration (3.0 mg) was less active. Furthermore, if the baseline ocular characteristics of the patients are carefully analyzed, there is a statistically significant difference between the lesions observed in the "best" group of patients, treated with the 0.3-mg dose, and the controls: both the size of choroidal neovascularization and the total lesion size were significantly greater (calculated with the use of Student's t-test) among the controls. Unfortunately, this result could in part explain the differences observed in the end points, since the size of the lesion appears to be more important than other baseline characteristics and larger lesions are associated with a worse prognosis.2 The authors should verify that the size of choroidal revascularization or the total size of the lesion is not a confounding factor in their interpretation.
Finally, what grounds do the authors have for suggesting that there is a reduction of neovascular progression with pegaptanib treatment? As shown in Table 4 of their article, the total size of the lesion or the size of choroidal revascularization actually increased by approximately 50 percent after 54 weeks, whatever the treatment.
Jean-Marie Rakic, M.D.
Pierre Blaise, M.D.
Jean-Michel Foidart, M.D.
University of Liege
Liege 4000, Belgium
jmrakic@ulg.ac.be
References
Gragoudas ES, Adamis AP, Cunningham EJ Jr, et al. Pegaptanib for neovascular age-related macular degeneration. N Engl J Med 2004;351:2805-2816.
Blinder KJ, Bradley S, Bressler NM, et al. Effect of lesion size, visual acuity, and lesion composition on visual acuity change with and without verteporfin therapy for choroidal neovascularization secondary to age-related macular degeneration: TAP and VIP report no. 1. Am J Ophthalmol 2003;136:407-418.
The authors reply: Dr. Rakic and colleagues pose three questions, to which we supply the following answers. With regard to the first question, the data indicate that all three doses of pegaptanib (0.3 mg, 1.0 mg, and 3.0 mg) are on the plateau of the dose–response curve. The combined analysis demonstrated the efficacy of all the doses, and there was no statistical difference between doses for the primary end point (P<0.05 for the comparison of each dose with usual care [i.e., sham injection or photodynamic therapy], and P>0.05 for each interdose comparison).
With respect to the second question, baseline measurements of the size of choroidal revascularization and the total size of the lesion differed slightly between the group receiving pegaptanib at a dose of 0.3 mg and the group receiving usual care. These differences were accounted for by prespecifying baseline measures such as lesion size as covariates in the statistical analyses of the primary end point. The cited post hoc exploratory meta-analysis of the use of photodynamic therapy suggested that patients with larger lesions lost more vision than those with smaller lesions.1 In contrast, multiple logistic-regression analysis of the data from the VEGF Inhibition Study in Ocular Neovascularization showed that patients receiving pegaptanib at a dose of 0.3 mg lost less vision, regardless of the size of choroidal revascularization or the lesion size. There is no evidence that the baseline differences in size had an effect on our results.
With regard to the third question, the average increase in the size of choroidal revascularization and the total size of the lesion from baseline to week 54 was less among patients treated with pegaptanib than among the controls receiving usual care.
Evangelos S. Gragoudas, M.D.
Massachusetts Eye and Ear Infirmary
Boston, MA 02114
evangelos_gragoudas@meei.harvard.edu
Anthony P. Adamis, M.D.
Matthew Feinsod, M.D.
Eyetech Pharmaceuticals
New York, NY 10036
Finally, what grounds do the authors have for suggesting that there is a reduction of neovascular progression with pegaptanib treatment? As shown in Table 4 of their article, the total size of the lesion or the size of choroidal revascularization actually increased by approximately 50 percent after 54 weeks, whatever the treatment.
Jean-Marie Rakic, M.D.
Pierre Blaise, M.D.
Jean-Michel Foidart, M.D.
University of Liege
Liege 4000, Belgium
jmrakic@ulg.ac.be
References
Gragoudas ES, Adamis AP, Cunningham EJ Jr, et al. Pegaptanib for neovascular age-related macular degeneration. N Engl J Med 2004;351:2805-2816.
Blinder KJ, Bradley S, Bressler NM, et al. Effect of lesion size, visual acuity, and lesion composition on visual acuity change with and without verteporfin therapy for choroidal neovascularization secondary to age-related macular degeneration: TAP and VIP report no. 1. Am J Ophthalmol 2003;136:407-418.
The authors reply: Dr. Rakic and colleagues pose three questions, to which we supply the following answers. With regard to the first question, the data indicate that all three doses of pegaptanib (0.3 mg, 1.0 mg, and 3.0 mg) are on the plateau of the dose–response curve. The combined analysis demonstrated the efficacy of all the doses, and there was no statistical difference between doses for the primary end point (P<0.05 for the comparison of each dose with usual care [i.e., sham injection or photodynamic therapy], and P>0.05 for each interdose comparison).
With respect to the second question, baseline measurements of the size of choroidal revascularization and the total size of the lesion differed slightly between the group receiving pegaptanib at a dose of 0.3 mg and the group receiving usual care. These differences were accounted for by prespecifying baseline measures such as lesion size as covariates in the statistical analyses of the primary end point. The cited post hoc exploratory meta-analysis of the use of photodynamic therapy suggested that patients with larger lesions lost more vision than those with smaller lesions.1 In contrast, multiple logistic-regression analysis of the data from the VEGF Inhibition Study in Ocular Neovascularization showed that patients receiving pegaptanib at a dose of 0.3 mg lost less vision, regardless of the size of choroidal revascularization or the lesion size. There is no evidence that the baseline differences in size had an effect on our results.
With regard to the third question, the average increase in the size of choroidal revascularization and the total size of the lesion from baseline to week 54 was less among patients treated with pegaptanib than among the controls receiving usual care.
Evangelos S. Gragoudas, M.D.
Massachusetts Eye and Ear Infirmary
Boston, MA 02114
evangelos_gragoudas@meei.harvard.edu
Anthony P. Adamis, M.D.
Matthew Feinsod, M.D.
Eyetech Pharmaceuticals
New York, NY 10036