{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T03:06:12Z","timestamp":1778814372315,"version":"3.51.4"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,6,12]],"date-time":"2021-06-12T00:00:00Z","timestamp":1623456000000},"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":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Inhibitors develop less frequently in haemophilia B (HB) than haemophilia A (HA). However, when present, the success of tolerization by immune tolerance induction (ITI) therapy is lower and the risk of complications higher.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To evaluate the use and outcome of ITI in patients with HB and inhibitors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Subjects include singletons or siblings with a current\/history of inhibitors enrolled in B\u2010Natural\u2014an observational study designed to increase understanding of clinical management of patients with HB. Patients were followed for 6 months and information on demographics, medical and social history, and treatment were recorded.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010nine patients with severe HB and inhibitors were enrolled in 24 centres. Twenty\u2010two underwent one or more courses of ITI with or without immune suppression. Eight patients (36.4%) were successfully tolerized after the first course of ITI. One of these successes (12.5%) experienced allergic manifestations, whereas the corresponding number for the 10 treatment failures was five (50%). One of seven (14.2%) patients with large deletions and three of eight (37.5%) with nonsense mutations were tolerized at the first attempt, and all patients experiencing nephrosis either failed or were on\u2010going. At study end, 11 (50%) were considered successfully tolerized after one or more ITI courses, three were unsuccessful, and eight were still undergoing treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data underscore the possibilities and difficulties of achieving tolerization in patients with HB with inhibitors. The type of mutation and complications appear to correlate with ITI outcome, but more accurate definitions of successful ITI are warranted.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.14357","type":"journal-article","created":{"date-parts":[[2021,6,12]],"date-time":"2021-06-12T14:01:45Z","timestamp":1623506505000},"page":"802-813","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The B\u2010Natural study\u2014The outcome of immune tolerance induction therapy in patients with severe haemophilia B"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8500-2483","authenticated-orcid":false,"given":"Jan","family":"Astermark","sequence":"first","affiliation":[{"name":"Department of Translational Medicine Lund University  Malm\u00f6 Sweden"},{"name":"Department of Haematology, Oncology and Radiation Physics Sk\u00e5ne University Hospital  Malm\u00f6 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Holstein","sequence":"additional","affiliation":[{"name":"Medical Department, Hemophilia Center University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasmina L.","family":"Abajas","sequence":"additional","affiliation":[{"name":"Hemophilia and Thrombosis Centre University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Kearney","sequence":"additional","affiliation":[{"name":"Children's Minnesota Centre for Bleeding and Clotting Disorders  Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6112-6166","authenticated-orcid":false,"given":"Stacy E.","family":"Croteau","sequence":"additional","affiliation":[{"name":"Boston Children's Hospital Boston Haemophilia Centre  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5659-554X","authenticated-orcid":false,"given":"Riana","family":"Liesner","sequence":"additional","affiliation":[{"name":"Great Ormond Street Hospital for Children NHS Trust supported by NIHR GOSH, BRC  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Funding","sequence":"additional","affiliation":[{"name":"Department of Haematology Institute of Clinical Medicine University Hospital Rigshospitalet University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2391-2016","authenticated-orcid":false,"given":"Christine L.","family":"Kempton","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine Emory University  Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suchitra","family":"Acharya","sequence":"additional","affiliation":[{"name":"Northwell Haemostasis and Thrombosis Centre  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Lethagen","sequence":"additional","affiliation":[{"name":"Sobi  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"LeBeau","sequence":"additional","affiliation":[{"name":"Rho, Inc.  Durham North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel","family":"Bowen","sequence":"additional","affiliation":[{"name":"Indiana Haemophilia and Thrombosis Centre  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2888-4931","authenticated-orcid":false,"given":"Erik","family":"Berntorp","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine Clinical Coagulation Research Lund University  Malm\u00f6 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2821-7159","authenticated-orcid":false,"given":"Amy D.","family":"Shapiro","sequence":"additional","affiliation":[{"name":"Indiana Haemophilia and Thrombosis Centre  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,6,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2017.08.007"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1660817"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.1999.00195.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01880.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2009.02039.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2006.01296.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2016.10.015"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.1999.t01-1-00303.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4613-0331-2_6"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.3.1115"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0049-3848(96)00136-3"},{"key":"e_1_2_8_13_1","article-title":"Natural history study of factor IX deficiency with focus on treatment and complications (B\u2010Natural)","author":"Shapiro AD","year":"2020","journal-title":"Haemophilia"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1615636"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1612943"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2007.01446.x"},{"issue":"10","key":"e_1_2_8_17_1","first-page":"48","article-title":"Immune tolerance induction and the treatment of hemophilia. 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