Systemic Complement Inhibition with Eculizumab for Geographic Atrophy in Age-Related Macular Degeneration

Systemic Complement Inhibition with Eculizumab for Geographic Atrophy in Age-Related Macular Degeneration

Author Yehoshua, Zohar Google Scholar
Garcia Filho, Carlos Alexandre de Amorim Autor UNIFESP Google Scholar
Nunes, Renata Portella Google Scholar
Gregori, Giovanni Google Scholar
Penha, Fernando M. Autor UNIFESP Google Scholar
Moshfeghi, Andrew A. Google Scholar
Zhang, Kang Google Scholar
Sadda, SriniVas Google Scholar
Feuer, William Google Scholar
Rosenfeld, Philip J. Google Scholar
Institution Univ Miami
Universidade Federal de São Paulo (UNIFESP)
Univ Calif San Diego
Univ So Calif
Abstract Purpose: To evaluate the effect of eculizumab, a systemic inhibitor of complement component (C5), on the growth of geographic atrophy (GA) in patients with age-related macular degeneration (AMD).Design: Prospective, double-masked, randomized clinical trial.Participants: Patients with GA measuring from 1.25 to 18 mm(2) based on spectral-domain optical coherence tomography imaging.Methods: Patients were randomized 2:1 to receive intravenous eculizumab or placebo over 6 months. in the eculizumab treatment arm, the first 10 patients received a low-dose regimen of 600 mg weekly for 4 weeks followed by 900 mg every 2 weeks until week 24, and the next 10 patients received a high-dose regimen of 900 mg weekly for 4 weeks followed by 1200 mg every 2 weeks until week 24. the placebo group was infused with saline. Patients were observed off treatment for an additional 26 weeks. Both normal-luminance and low-luminance visual acuities were measured throughout the study, and the low-luminance deficits were calculated as the difference between the letter scores.Main Outcome Measures: Change in area of GA at 26 weeks.Results: Thirty eyes of 30 patients were enrolled. Eighteen fellow eyes also met inclusion criteria and were analyzed as a secondary endpoint. for the 30 study eyes, mean square root of GA area measurements +/-standard deviation at baseline were 2.55+/-0.94 and 2.02+/-0.74 mm in the eculizumab and placebo groups, respectively (P = 0.13). At 26 weeks, GA enlarged by a mean of 0.19+/-0.12 and 0.18+/-0.15 mm in the eculizumab and placebo groups, respectively (P = 0.96). At 52 weeks of follow-up, GA enlarged by a mean of 0.37+/-0.22 mm in the eculizumab-treated eyes and by a mean of 0.37+/-0.21 mm in the placebo group (P = 0.93, 2 sample t test). None of the eyes converted to wet AMD. No drug-related adverse events were identified.Conclusions: Systemic complement inhibition with eculizumab was well tolerated through 6 months but did not decrease the growth rate ofGAsignificantly. However, there was a statistically significant correlation between the low-luminance deficit at baseline and the progression of GA over 6 months. (C) 2014 by the American Academy of Ophthalmology.
Language English
Sponsor Alexion Pharmaceuticals
Macula Vision Research Foundation
Carl Zeiss Meditec, Inc., Dublin, California
Research to Prevent Blindness, Inc., New York, New York
National Eye Institute, National Institutes of Health, Bethesda, Maryland
Department of Defense, Washington, DC
Jerome A. Yavitz Charitable Foundation
Emma Clyde Hodge Memorial Foundation
Florman Family Foundation, Inc.
Gemcon Family Foundation
Grant number National Eye Institute, National Institutes of Health, Bethesda, Maryland: P30 EY014801
Department of Defense, Washington, DC: W81XWH-09-10675
Date 2014-03-01
Published in Ophthalmology. New York: Elsevier B.V., v. 121, n. 3, p. 693-701, 2014.
ISSN 0161-6420 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 693-701
Origin http://dx.doi.org/10.1016/j.ophtha.2013.09.044
Access rights Closed access
Type Article
Web of Science ID WOS:000332401800019
URI http://repositorio.unifesp.br/handle/11600/37497

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