{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:07:46Z","timestamp":1787314066740,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T00:00:00Z","timestamp":1694476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["NWA.1160.18.038"],"award-info":[{"award-number":["NWA.1160.18.038"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Recombinant factor IX Fc fusion protein (rFIX\u2010Fc) is an extended half\u2010life factor concentrate administered to haemophilia B patients. So far, a population pharmacokinetic (PK) model has only been published for patients aged \u226512\u2009years. The aim was to externally evaluate the predictive performance of the published rFIX\u2010Fc population PK model for patients of all ages and develop a model that describes rFIX\u2010Fc PK using real\u2010world data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We collected prospective and retrospective data from patients with haemophilia B treated with rFIX\u2010Fc and included in the OPTI\u2010CLOT TARGET study (NTR7523) or United Kindom (UK)\u2010EHL Outcomes Registry (NCT02938156). Predictive performance was assessed by comparing predicted with observed FIX activity levels. A new population PK model was constructed using nonlinear mixed\u2010effects modelling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Real\u2010world data were obtained from 37 patients (median age: 16\u2009years, range 2\u201371) of whom 14 were aged &lt;12\u2009years. Observed FIX activity levels were significantly higher than levels predicted using the published model, with a median prediction error of \u221248.8%. The new model showed a lower median prediction error (3.4%) and better described rFIX\u2010Fc PK, especially for children aged &lt;12\u2009years. In the new model, an increase in age was correlated with a decrease in clearance (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u2009.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The published population PK model significantly underpredicted FIX activity levels. The new model better describes rFIX\u2010Fc PK, especially for children aged &lt;12\u2009years. This study underlines the necessity to strive for representative population PK models, thereby avoiding extrapolation outside the studied population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcp.15881","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T21:33:36Z","timestamp":1691789616000},"page":"220-231","source":"Crossref","is-referenced-by-count":5,"title":["A new population pharmacokinetic model for recombinant factor IX\u2010Fc fusion concentrate including young children with haemophilia B"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4536-2692","authenticated-orcid":false,"given":"Sjoerd F.","family":"Koopman","sequence":"first","affiliation":[{"name":"Hospital Pharmacy\u2010Clinical Pharmacology Amsterdam University Medical Centers  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tine M.H.J.","family":"Goedhart","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Erasmus MC Sophia Children's Hospital University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7967-1023","authenticated-orcid":false,"given":"Laura H.","family":"Bukkems","sequence":"additional","affiliation":[{"name":"Hospital Pharmacy\u2010Clinical Pharmacology Amsterdam University Medical Centers  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor M.","family":"Mulders","sequence":"additional","affiliation":[{"name":"Hospital Pharmacy\u2010Clinical Pharmacology Amsterdam University Medical Centers  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank W.G.","family":"Leebeek","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus MC University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Fijnvandraat","sequence":"additional","affiliation":[{"name":"Amsterdam UMC University of Amsterdam, Emma Children's Hospital, Pediatric Hematology  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel","family":"Coppens","sequence":"additional","affiliation":[{"name":"Vascular Medicine, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"},{"name":"Amsterdam Cardiovascular Sciences Pulmonary Hypertension &amp; Thrombosis  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Mathias","sequence":"additional","affiliation":[{"name":"Haemophilia Comprehensive Care Centre Great Ormond Street Hospital for Children NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter W.","family":"Collins","sequence":"additional","affiliation":[{"name":"Arthur Bloom Haemophilia Centre, School of Medicine Cardiff University Hospital  Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Campbell","family":"Tait","sequence":"additional","affiliation":[{"name":"Department of Haematology Glasgow Royal Infirmary  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine N.","family":"Bagot","sequence":"additional","affiliation":[{"name":"Department of Haematology Glasgow Royal Infirmary  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Curry","sequence":"additional","affiliation":[{"name":"Oxford Haemophilia and Thrombosis Centre and Oxford NIHR BRC Nuffield Orthopaedic Hospital  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanette","family":"Payne","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology Sheffield Children's NHS Foundation Trust  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pratima","family":"Chowdary","sequence":"additional","affiliation":[{"name":"Katharine Dormandy Haemophilia Centre and Thrombosis Unit Royal Free London NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjon H.","family":"Cnossen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Erasmus MC Sophia Children's Hospital University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron A.A.","family":"Math\u00f4t","sequence":"additional","affiliation":[{"name":"Hospital Pharmacy\u2010Clinical Pharmacology Amsterdam University Medical Centers  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the OPTI\u2010CLOT study group and SYMPHONY 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