A Baseline Score to Predict Response to Ranibizumab Treatment in Neovascular Age-Related Macular Degeneration

Abstract

Purpose What are the patient characteristics predictive of response to ranibizumab treatment? Methods Model-based characterization of best-corrected visual acuity (BCVA) time profiles of patients with neovascular age-related macular degeneration under ranibizumab or sham treatment based on 24-month observations of BCVA in 2419 patients from randomized multicenter phase 3 trials of ranibizumab: ANCHOR, MARINA, PIER, and HARBOR. Goodness-of-fit plots and precision of parameter estimates were used for measure of accuracy. Results The model incorporates a long-term effect on disease progression and an additive and more potent short-term effect of ranibizumab. Response to ranibizumab treatment and progression of the disease were found to be a function of seven baseline characteristics (visual acuity, age, leakage size, central retinal lesion thickness, presence or absence of cyst, type of choroidal neovascularization (CNV), and size of pigment epithelium detachment). A composite score of these seven baseline characteristics was derived and used to categorize response to ranibizumab treatment. The ranibizumab treatment arms of two proof-of-concept studies held out from the model development were used to validate the methodology. Conclusions A composite score based on seven patient characteristics prior to treatment could be used to discriminate patients with predicted insufficient response to anti–vascular endothelial growth factor treatment. Translational Relevance The method could be used to create a virtual ranibizumab treatment arm in clinical trials or to reduce the size of a ranibizumab active control arm.