Systemic complement inhibition with eculizumab for geographic atrophy in age-related macular degeneration: the COMPLETE study

Z Yehoshua, CA de Amorim Garcia Filho, RP Nunes… - Ophthalmology, 2014 - Elsevier
Z Yehoshua, CA de Amorim Garcia Filho, RP Nunes, G Gregori, FM Penha, AA Moshfeghi
Ophthalmology, 2014Elsevier
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 …
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 mm2 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 of GA significantly. However, there was a statistically significant correlation between the low-luminance deficit at baseline and the progression of GA over 6 months.
Elsevier