{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T06:31:40Z","timestamp":1783405900936,"version":"3.54.6"},"reference-count":32,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,8,15]],"date-time":"2018-08-15T00:00:00Z","timestamp":1534291200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Novartis Pharma AG"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:p>Intravitreal ranibizumab is a first\u2010line therapy for neovascular age\u2010related macular degeneration (<jats:styled-content style=\"fixed-case\">nAMD<\/jats:styled-content>), 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\u2010vascular endothelial growth factor (<jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>) treatment\u2010na\u00efve patients. A total of 1,524 treatment\u2010na\u00efve patients and 29,754 visual acuity observations from the <jats:styled-content style=\"fixed-case\">ANCHOR<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> MARINA<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> PIER<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">EXCITE<\/jats:styled-content> clinical trials informed the model. The model accurately described natural <jats:styled-content style=\"fixed-case\">nAMD<\/jats:styled-content> disease progression and predicted mean visual acuity gains in the <jats:styled-content style=\"fixed-case\">HARBOR<\/jats:styled-content> study, notably with a 2.0\u00a0mg ranibizumab dose not used for model development. Furthermore, individualized treatment regimens were shown by simulation to be a viable alternative to the commonly used <jats:italic>pro re nata<\/jats:italic> or fixed monthly dosing regimen approaches. Therefore, this model could be a useful tool to predict the outcomes of different, more patient\u2010tailored treatment regimens in <jats:styled-content style=\"fixed-case\">nAMD<\/jats:styled-content>.<\/jats:p>","DOI":"10.1002\/psp4.12322","type":"journal-article","created":{"date-parts":[[2018,7,25]],"date-time":"2018-07-25T04:25:26Z","timestamp":1532492726000},"page":"660-669","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Neovascular Age\u2010Related Macular Degeneration: A Visual Acuity Model of Natural Disease Progression and Ranibizumab Treatment Effect"],"prefix":"10.1002","volume":"7","author":[{"given":"Zufar","family":"Mulyukov","sequence":"first","affiliation":[{"name":"Novartis Pharma AG  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Weber","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Pigeolet","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Clemens","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG  Basel Switzerland"},{"name":"Faculty of Medicine Cardiology and Angiology I Heart Center Freiburg University  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Lehr","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Saarland University  Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Racine","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,15]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.06.018"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-013-2562-6"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.124.4.529"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2011.05.011"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2011.07.019"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-3768.2011.02179.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa062655"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0420.2006.00736.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.iae.0000242842.14624.e7"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2007.05.008"},{"key":"e_1_2_10_11_1","unstructured":"Genentech.Lucentis\u00ae(ranibizumab injection) for intravitreal injection. Biologic License Application (BLA): 125156. U.S. Food & Drug Administration. <https:\/\/www.accessdata.fda.gov\/scripts\/cder\/daf\/index.cfm?event=overview.process&varApplNo=125156> (2006). Accessed March 2018."},{"key":"e_1_2_10_12_1","unstructured":"Novartis.Lucentis (ranibizumab). EMEA\/H\/C\/000715. European Medicines Agency. <http:\/\/www.ema.europa.eu\/ema\/index.jsp?curl=pages\/medicines\/human\/medicines\/000715\/human_med_000890.jsp&mid=WC0b01ac058001d124> (2008). 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