Open AccessNeovascular Age‐Related Macular Degeneration: A Visual Acuity Model of Natural Disease Progression and Ranibizumab Treatment Effect
Author(s) -
Mulyukov Zufar,
Weber Sebastian,
Pigeolet Etienne,
Clemens Andreas,
Lehr Thorsten,
Racine Amy
Publication year - 2018
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1002/psp4.12322
Subject(s) - ranibizumab , macular degeneration , medicine , pro re nata , visual acuity , ophthalmology , dosing , regimen , disease , clinical trial , natural history , bevacizumab , chemotherapy
Intravitreal ranibizumab is a first‐line therapy for neovascular age‐related macular degeneration ( nAMD ), but there is a need to optimize patient outcomes while minimizing treatment burden. Here, we developed an indirect response, nonlinear, mixed effects model of disease progression and drug effect in anti‐vascular endothelial growth factor ( VEGF ) treatment‐naïve patients. A total of 1,524 treatment‐naïve patients and 29,754 visual acuity observations from the ANCHOR , MARINA , PIER , and EXCITE clinical trials informed the model. The model accurately described natural nAMD disease progression and predicted mean visual acuity gains in the HARBOR study, notably with a 2.0 mg ranibizumab dose not used for model development. Furthermore, individualized treatment regimens were shown by simulation to be a viable alternative to the commonly used pro re nata or fixed monthly dosing regimen approaches. Therefore, this model could be a useful tool to predict the outcomes of different, more patient‐tailored treatment regimens in nAMD .