{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:58:18Z","timestamp":1790621898874,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired haematopoietic stem cell disorder. Crovalimab, a complement C5\u2010inhibitor, is approved for PNH and can be self\u2010administered subcutaneously every 4\u00a0weeks, offering a more convenient route than intravenous C5\u2010inhibitors. Since exposure often exceeds pharmacokinetic targets and varies with body weight, we aimed to explored individualized dosing of crovalimab using clinical trial simulations to optimize therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We compared standard, weight\u2010based and therapeutic drug monitoring (TDM)\u2010guided regimens in treatment\u2010na\u00efve PNH patients over 52\u2009weeks by means of clinical trial simulations based on the population pharmacokinetic model developed by the market authorization holder.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Maintenance\u2010phase crovalimab concentrations were generally supratherapeutic with substantial variability. Weight\u2010based dosing reduced this variability, while TDM\u2010guided dosing further minimized it and allowed dose intervals to be prolonged in 24% of patients to a mean of 5.0\u00a0weeks, while maintaining exposure comparable to the standard regimen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Individualized dosing of crovalimab may reduce exposure variability and enable less frequent dosing, supporting the feasibility of more flexible cost\u2010effective and patient\u2010tailored treatment regimens.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70651","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T01:55:38Z","timestamp":1781488538000},"page":"3460-3465","source":"Crossref","is-referenced-by-count":0,"title":["Exploring individualized crovalimab dosing in PNH through in silico modelling: Potential for improved convenience and cost efficiency"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5757-4919","authenticated-orcid":false,"given":"Mendy","family":"ter Avest","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Pharmacology &amp; Toxicology Radboudumc  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7011-667X","authenticated-orcid":false,"given":"Simon E.","family":"Koele","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmacology &amp; Toxicology Radboudumc  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole C. A. J.","family":"van de Kar","sequence":"additional","affiliation":[{"name":"Department of Paediatric Nephrology Radboudumc  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia M. C.","family":"Langemeijer","sequence":"additional","affiliation":[{"name":"Department of Haematology Radboudumc  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2185-8201","authenticated-orcid":false,"given":"Rob","family":"ter Heine","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmacology &amp; Toxicology Radboudumc  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102014\u201002\u2010522128"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102007\u201006\u2010094136"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102018\u201009\u2010876136"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2029073"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2308695"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.27412"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010024\u201002023\u20106"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/0272989X14539731"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/13696998.2020.1831519"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102021\u2010153190"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102023\u2010188063"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.770640"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.27413"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.16394"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102020\u2010134590"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-136265"},{"key":"e_1_2_9_18_1","unstructured":"Food and Drug Administration (FDA).Drug approval package Piasky (crovalimab).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2024\/761388Orig1s000IntegratedR.pdfaccessed on July 21 2025."},{"key":"e_1_2_9_19_1","unstructured":"Centers for Disease Control and Prevention (CDC).National Center for Health Statistics (NCHS).National health and nutrition examination survey data. US Department of Health and Human Services Centers for Disease Control and Prevention."},{"key":"e_1_2_9_20_1","volume-title":"A language and environment for statistical computing","author":"R Core Team","year":"2024"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.24"},{"key":"e_1_2_9_22_1","volume-title":"RStudio: integrated development for R","author":"RStudio Team","year":"2025"},{"key":"e_1_2_9_23_1","unstructured":"NICE.NICE Technology appraisal guidance\u2014crovalimab for treating paroxysmal nocturnal haemoglobinuria in people 12 years and over2024.https:\/\/www.nice.org.uk\/guidance\/ta1019"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15537"},{"key":"e_1_2_9_25_1","unstructured":"Food and Drug Administration (FDA).Drug approval package Fabhalta (iptacopan hydrochloride).https:\/\/www.accessdata.fda.gov\/scripts\/cder\/daf\/index.cfm?event=BasicSearch.process. 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