{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T20:41:31Z","timestamp":1780432891060,"version":"3.54.1"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:00:00Z","timestamp":1666310400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Emicizumab promotes effective haemostasis in people with haemophilia A (PwHA). It is indicated for routine prophylaxis of bleeding episodes in PwHA with or without factor (F)VIII inhibitors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To investigate the effect of emicizumab dose up\u2010titration in PwHA with suboptimal bleeding control.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data from seven completed or ongoing phase III studies were pooled. Pharmacokinetics, pharmacodynamics and bleeding events were evaluated before and after dose up\u2010titration. Adverse events (AEs) were compared between PwHA with and without dose up\u2010titration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 675 PwHA evaluable for the analysis, 24 (3.6%) had their maintenance dose up\u2010titrated to 3\u00a0mg\/kg once weekly (QW). Two participants had neutralising antibodies (nAbs) associated with decreased emicizumab exposure, and dose increase did not compensate for the effect of nAbs. In the other 22 participants, mean emicizumab steady\u2010state trough concentrations increased from 44.0 to 86.2\u00a0\u03bcg\/mL after up\u2010titration. The median (interquartile range [IQR]) efficacy period prior to up\u2010titration was 24.6 (24.0\u201332.0) weeks. The model\u2010based annualised bleed rate for \u2018treated bleeds\u2019 and \u2018all bleeds\u2019 decreased by 70.2% and 72.9%, respectively, after a median (IQR) follow\u2010up of 97.1 (48.4\u2013123.3) weeks in the up\u2010titration period. Incidences of injection\u2010site reactions and serious AEs were higher in PwHA with up\u2010titration; however, this was already observed in these participants before the dose up\u2010titration. Overall, the safety profile appeared similar between PwHA with and without up\u2010titration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The dose up\u2010titration to 3\u00a0mg\/kg QW was well tolerated. Bleed control improved in most participants whose bleeding tendency was inadequately controlled during clinical trials.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.14679","type":"journal-article","created":{"date-parts":[[2022,10,22]],"date-time":"2022-10-22T04:10:40Z","timestamp":1666411840000},"page":"90-99","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Emicizumab dose up\u2010titration in case of suboptimal bleeding control in people with haemophilia A"],"prefix":"10.1111","volume":"29","author":[{"given":"Christophe","family":"Schmitt","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology F. Hoffmann\u2010La Roche Ltd  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Elisa","family":"Mancuso","sequence":"additional","affiliation":[{"name":"IRCCS Humanitas Research Hospital Center for Thrombosis and Hemorrhagic Diseases  Rozzano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Chang","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"},{"name":"Spark Therapeutics, Inc.  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Podolak\u2010Dawidziak","sequence":"additional","affiliation":[{"name":"Department of Haematology Blood Neoplasms and Bone Marrow Transplantation Wroclaw Medical University  Wroc\u0142aw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Petry","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology F. Hoffmann\u2010La Roche Ltd  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Sidonio Jr","sequence":"additional","affiliation":[{"name":"Children's Healthcare of Atlanta Emory University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Yoneyama","sequence":"additional","affiliation":[{"name":"Chugai Pharmaceutical Co., Ltd  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel S.","family":"Key","sequence":"additional","affiliation":[{"name":"Department of Medicine and Blood Research Center University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Niggli","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology F. Hoffmann\u2010La Roche Ltd  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Lehle","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology F. Hoffmann\u2010La Roche Ltd  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"Peyvandi","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico Angelo Bianchi Bonomi Hemophilia and Thrombosis Center  Milan Italy"},{"name":"Department of Pathophysiology and Transplantation Universit\u00e0 degli Studi di Milano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Oldenburg","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,10,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200106073442307"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14046"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.15256\/joc.2011.1.2"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2942"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1511769"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1703068"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019001869"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1803550"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(19)30054-7"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/rth2.12670"},{"key":"e_1_2_9_12_1","author":"Jim\u00e9nez\u2010Yuste V","year":"2022","journal-title":"Res Prac Thromb Haemost"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13848"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13495"},{"key":"e_1_2_9_15_1","unstructured":"European MedicinesAgency HEMLIBRA\u00ae solution for injection: emicizumab piIEa. Initial EU approval: 2018.2019. Accessed October 2022.https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/hemlibra\u2010epar\u2010product\u2010information_en.pdf"},{"key":"e_1_2_9_16_1","unstructured":"Food andDrug Administration.HEMLIBRA\u00ae (emicizumab\u2010kxwh) injection for subcutaneous use prescribing information[Initial U.S. approval: 2017].2018. Accessed Octobery 2022.https:\/\/www.gene.com\/download\/pdf\/hemlibra_prescribing.pdf"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1615621"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14257"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-020-00904-z"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14398"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0040-1717114"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14205"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-017-0616-3"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1968"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10194303"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2021.100852"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-021-01006-0"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009217"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyh299"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12672"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.14679","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hae.14679","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.14679","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T22:16:11Z","timestamp":1692310571000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.14679"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,21]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1]]}},"alternative-id":["10.1111\/hae.14679"],"URL":"https:\/\/doi.org\/10.1111\/hae.14679","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,21]]},"assertion":[{"value":"2022-06-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}