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M. Neuner-Jehle, B. Scassellati-Sforzolini, T. P. Dryja, C. Paulding, S. Lewitzky, Y. He, L. Farrer, J. Meyer; Clinical Pharmacogenetic Analysis of Patients With Neovascular AMD Treated With Ranibizumab in the EXCITE Trial. Invest. Ophthalmol. Vis. Sci. 2009;50(13):722.
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Explore correlation between genetic polymorphisms in patients with neovascular AMD and their best-corrected visual acuity (BCVA) response to ranibizumab.
In the double-masked, active-controlled, multi-center EXCITE study 353 AMD patients were randomized into 3 treatment groups: 3 consecutive monthly injections (loading phase) followed by quarterly injections of 0.3 mg ranibizumab (n=120); loading phase and quarterly injections of 0.5 mg ranibizumab (n=118); monthly 0.3 mg ranibizumab injections (n=115). Primary endpoint: change in mean BCVA (Early Treatment for Diabetic Retinopathy Study charts) from baseline to Month 12. 114 patients consented to pharmacogenetic assessment and were genotyped for 11 genetic variants in 5 genes known to be associated with AMD (e.g. CFH, BF, C2, C3, and ARMS2), and were included in the association analysis using a linear regression model. For the analysis of extreme responders (gain or loss of at least 15 letters from baseline to Month 12), descriptive statistics were provided.
No overall association between the genetic variants and the primary endpoint was found. For extreme responders, the Tyr402His variant in the complement factor H (CFH) gene was found to show a numerical trend towards an association with ranibizumab response rates (CC/CT/TT = 100/94/63%) over all treatment groups. Patients with CC and CT genotypes tended to have greater mean improvement in BCVA from baseline to Month 12 (both 7.9 letters) compared to those with the TT genotype (3.9 letters).
Our study did not find disease markers with a large effect on ranibizumab response. Patients with the Tyr402His variant showed a trend toward differential response to ranibizumab. This association was not statistically significant, although statistical power of this study was limited by small sample size. Further studies of ongoing clinical trials are needed to evaluate this potential association.
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