{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T21:29:29Z","timestamp":1790890169292,"version":"4.1.0"},"reference-count":21,"publisher":"American Society of Hematology","issue":"16","license":[{"start":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:00:00Z","timestamp":1675382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,4,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Inhibitor development remains a major challenge in factor VIII (FVIII) replacement therapy. verITI-8 is the first prospective study of a recombinant FVIII Fc fusion protein (rFVIIIFc; efmoroctocog alfa) for first-time immune tolerance induction (ITI) in males with severe hemophilia A and high-titer inhibitors (historical peak \u22655 Bethesda units [BU]\/mL). In this single-arm, open-label, multicenter study, screening was followed by ITI (rFVIIIFc 200 IU\/kg per day until tolerization or maximum of 48 weeks). Those who achieved ITI success entered a tapering period, returning to standard prophylaxis, and then entered follow-up. Primary end point was time to tolerization with rFVIIIFc defined by inhibitor titer &amp;lt;0.6 BU\/mL, incremental recovery (IR) \u226566% of expected IR (IR \u22651.32 IU\/dL per IU\/kg), and half-life (t\u00bd) \u22657 hours within 48 weeks. Sixteen patients received \u22651 rFVIIIFc dose. Twelve (75%), 11 (69%), and 10 patients (63%), respectively, achieved negative inhibitor titers, an IR \u226566%, and a t\u00bd \u22657 hours (ie, tolerance) within 48 weeks. Median times in weeks to achieve these markers of success were 7.4 (interquartile range [IQR], 2.2-17.8), 6.8 (IQR, 5.4-22.4), and 11.7 (IQR, 9.8-26.2), respectively. All patients experienced \u22651 treatment-emergent adverse event (TEAE), and 1 reported \u22651 related TEAE (injection site pain). Nine patients experienced \u22651 treatment-emergent serious AE. No thrombotic events, discontinuations because of AEs, or deaths were reported during the study. As the first extended half-life rFVIII with prospective data in ITI, rFVIIIFc offered short time to tolerization with durable responses in almost two-thirds of patients and was well tolerated. This trial was registered at www.clinicaltrials.gov as #NCT03093480.<\/jats:p>","DOI":"10.1182\/blood.2022017780","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T21:05:25Z","timestamp":1675458325000},"page":"1982-1989","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":20,"title":["Recombinant factor VIII Fc fusion protein for first-time immune tolerance induction: final results of\u00a0the verITI-8 study"],"prefix":"10.1182","volume":"141","author":[{"given":"Lynn","family":"Malec","sequence":"first","affiliation":[{"name":"1Versiti Blood Research Institute, Milwaukee, WI"},{"name":"2Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Van Damme","sequence":"additional","affiliation":[{"name":"3Cliniques Universitaires Saint-Luc, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1551-3995","authenticated-orcid":false,"given":"Anthony K. 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MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8436-1780","authenticated-orcid":false,"given":"Stefan","family":"Lethagen","sequence":"additional","affiliation":[{"name":"7Sobi, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5350-1763","authenticated-orcid":false,"given":"Manuel","family":"Carcao","sequence":"additional","affiliation":[{"name":"8Division of Haematology\/Oncology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7423-9864","authenticated-orcid":false,"given":"Flora","family":"Peyvandi","sequence":"additional","affiliation":[{"name":"9Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy"},{"name":"10Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"suppl 6","key":"2023110216021379600_bib1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/hae.14046","article-title":"WFH guidelines for the management of hemophilia, 3rd edition","volume":"26","author":"Srivastava","year":"2020","journal-title":"Haemophilia"},{"issue":"2","key":"2023110216021379600_bib2","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/hae.13413","article-title":"Recombinant factor VIII Fc fusion protein for immune tolerance induction in patients with severe haemophilia A with inhibitors-A retrospective analysis","volume":"24","author":"Carcao","year":"2018","journal-title":"Haemophilia"},{"issue":"1","key":"2023110216021379600_bib3","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/hae.14192","article-title":"Real-world data of immune tolerance induction using recombinant factor VIII Fc fusion protein in 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