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Henry Wiley, Clare Bailey, Catherine A Cukras, Glenn J Jaffe, Richard W J Lee, Erin Loken, Catherine Meyerle, Darby J.S. Thompson, Wai T Wong, Frederick L Ferris; A randomized 36-week crossover trial comparing ranibizumab and bevacizumab for diabetic macular edema. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3149.
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Ranibizumab and bevacizumab are widely used to treat diabetic macular edema (DME), and their comparative efficacy is being evaluated in a large trial by the Diabetic Retinopathy Clinical Research Network (DRCR.net). We tested the comparative efficacy of ranibizumab and bevacizumab in a randomized 36-week crossover trial, to explore whether this study design would allow meaningful and efficient comparison using a smaller sample size than required for a traditional parallel group trial.
In this randomized, double-masked, 36-week, three-period crossover clinical trial, we compared the efficacy of monthly intravitreous injections of ranibizumab and bevacizumab for treatment of DME involving the center of the macula in 56 subjects. Comparisons are made through a linear mixed-effect model, adjusting for period, clinical site, baseline visual acuity, and multiple observations within subject. Mean changes in visual acuity and central retinal thickness are estimated based on the model.
Based on the linear mixed-effect model, the three-month estimated mean improvement in visual acuity was 5.3 letters for bevacizumab and 6.6 letters for ranibizumab, with a difference of 1.3 letters (p = 0.039). Model-based comparisons of change in optical coherence tomography (OCT) central subfield mean thickness (CSMT) showed a mean change of -89 µm for bevacizumab and -137 µm for ranibizumab, with a difference of 48 µm (p < 0.001).<br /> <br /> Combining the period and treatment effects in the model yields a predicted 36-week (9-month) average improvement in visual acuity of 7.1 letters (95% CI [5.0, 9.2]) for bevacizumab and 8.4 letters (95% CI [6.3, 10.5]) for ranibizumab, and a predicted 36-week average change in OCT CSMT of -128 µm (95% CI [-155, -100]) for bevacizumab and -176 µm (95% CI [-202, -149]) for ranibizumab.<br /> <br /> There were no statistically significant differential carry-over effects or treatment by period interactions.
This trial demonstrates a statistically significant but small relative clinical benefit of ranibizumab compared with bevacizumab for treatment of DME, using a reduced sample size relative to a full comparative efficacy study, suggesting that this design might be useful for future comparisons of anti-vascular endothelial growth factor drugs. Report of the concurrent trial by the DRCR.net will provide an opportunity to compare findings from the two different study designs.
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