{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T07:40:40Z","timestamp":1768894840941,"version":"3.49.0"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The tyrosine kinase inhibitor, nintedanib, reduces the rate of decline in forced vital capacity (FVC) in a comparable manner in patients with idiopathic pulmonary fibrosis (IPF), other forms of progressive pulmonary fibrosis (PPF), and systemic sclerosis\u2010associated ILD (SSc\u2010ILD). The recommended dose of nintedanib in all indications is 150\u2009mg twice daily (BID). Data from Phase II and III trials in IPF, PPF, and SSc\u2010ILD were incorporated into a meta\u2010model to holistically investigate the relationship between nintedanib exposure and efficacy. Using data from 2642 patients with IPF, PPF, or SSc\u2010ILD treated with nintedanib doses ranging from 50 to 150\u2009mg BID, disease progression models with a maximum drug effect on the annual rate of change in absolute FVC (i.e., mL), FVC %predicted, and FVC Z\u2010score were developed. The estimated plasma concentration producing 50% of the maximum drug effect (EC\n                    <jats:sub>50<\/jats:sub>\n                    ) ranged from 6.21 to 10.4\u2009nM (with respect to nintedanib trough concentration) across the explored FVC\u2010based endpoints. While the disease progression for absolute FVC (mL), FVC %predicted, and FVC Z\u2010score was different between IPF and PPF patients compared to SSc\u2010ILD patients, the relative treatment effect of nintedanib, described by a disease\u2010modifying E\n                    <jats:sub>max<\/jats:sub>\n                    effect, was comparable across indications. The majority of patients achieve exposure levels at or exceeding the EC\n                    <jats:sub>50<\/jats:sub>\n                    with the approved starting dose of 150\u2009mg BID.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70132","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T11:49:27Z","timestamp":1763725767000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exposure\u2010Efficacy Meta\u2010Model of Nintedanib in Adult Patients With Chronic Fibrosing Interstitial Lung Diseases"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0693-0562","authenticated-orcid":false,"given":"Sonja","family":"Hartmann","sequence":"first","affiliation":[{"name":"Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharmaceuticals, Inc.  Ridgefield Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Janssen","sequence":"additional","affiliation":[{"name":"Pharmetheus AB  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3572-9711","authenticated-orcid":false,"given":"Jakob","family":"Ribbing","sequence":"additional","affiliation":[{"name":"Pharmetheus AB  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6013-0225","authenticated-orcid":false,"given":"Susanne","family":"Stowasser","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International GmbH  Ingelheim am Rhein Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3807-3323","authenticated-orcid":false,"given":"Julia","family":"Korell","sequence":"additional","affiliation":[{"name":"Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharmaceuticals, Inc.  Ridgefield Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"European Medicines Agency \u201cOfev (European Public Assessment Report) \u201d2020 https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/ofev."},{"key":"e_1_2_9_3_1","unstructured":"U.S. Food & Drug Administration \u201cOFEV (Nintedanib): Prescribing Information \u201d2020 https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/205832s013lbl.pdf."},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402584"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1103690"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2016-209701"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2016.02.001"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1903076"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1908681"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2021.106369"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjresp-2017-000212"},{"issue":"4","key":"e_1_2_9_12_1","first-page":"75","article-title":"S.T. 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