{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T14:43:04Z","timestamp":1789915384678,"version":"4.0.1"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,7,23]],"date-time":"2015-07-23T00:00:00Z","timestamp":1437609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004702","name":"Baxter International","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004702","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004326","name":"Bayer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008322","name":"CSL Behring","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006314","name":"Biogen Idec","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006314","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec><jats:title>Introduction\/background<\/jats:title><jats:p>Development of neutralizing inhibitors against factor VIII (FVIII) is a major complication of haemophilia A treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>The ongoing, international, open\u2010label, uncontrolled, observational immune tolerance induction (ObsITI) study evaluates <jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content>, the standard of care in patients with inhibitors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients\/methods<\/jats:title><jats:p>Forty\u2010eight prospective patients in this interim analysis received a single plasma\u2010derived, von Willebrand factor\u2010stabilized, FVIII concentrate (pdFVIII\/VWF) for <jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content>. According to recommended Bonn protocol, \u2018low responders\u2019 at <jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content> start (&lt;5\u00a0BU) received 50\u2013100\u00a0IU FVIII\u00a0kg<jats:sup>\u22121<\/jats:sup> daily, or every other day; \u2018high responders\u2019 (\u22655\u00a0BU) received 100\u00a0IU FVIII\u00a0kg<jats:sup>\u22121<\/jats:sup> every 12\u00a0h.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Forty of 48 patients (83.3%), had <jats:italic>at least<\/jats:italic> one risk factor for poor <jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content>\u2010prognosis at <jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content> start (i.e. age \u22657\u00a0years, &gt;2\u00a0years since inhibitor diagnosis, inhibitor titre \u226510\u00a0BU at the start of <jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content>, or prior <jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content> failure). Nonetheless, 34 patients (70.8%) achieved <jats:italic>complete success<\/jats:italic>, 3 (6.3%) <jats:italic>partial success<\/jats:italic>, 1 (2.1%) <jats:italic>partial response<\/jats:italic>;<jats:styled-content style=\"fixed-case\"> ITI<\/jats:styled-content> failed in 10 patients (20.8%), all with poor prognosis factors. All six low responders achieved <jats:italic>complete success<\/jats:italic>. <jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content> outcome was significantly associated with inhibitor titre level at <jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content> start (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0068), number of poor prognosis factors for <jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content> success (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0187), monthly bleeding rate during <jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content> (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0005) and peak inhibitor titre during <jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content> (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0007). Twenty\u2010two of 35 high responder patients (62.9%) with \u22651 poor prognosis factor achieved <jats:italic>complete success<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Treatment with a single pdFVIII\/VWF concentrate, mainly according to the Bonn protocol, resulted in a high <jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content> success rate in haemophilia A patients with inhibitors and poor prognosis for <jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content> success.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.12774","type":"journal-article","created":{"date-parts":[[2015,7,23]],"date-time":"2015-07-23T05:51:07Z","timestamp":1437630667000},"page":"87-95","source":"Crossref","is-referenced-by-count":52,"title":["First prospective report on immune tolerance in poor risk haemophilia A inhibitor patients with a single factor VIII\/von Willebrand factor concentrate in an observational immune tolerance induction study"],"prefix":"10.1111","volume":"22","author":[{"given":"W.","family":"Kreuz","sequence":"first","affiliation":[{"name":"HZRM H\u00e4mophilie\u2010Zentrum Rhein Main Frankfurt\u2010M\u00f6rfelden M\u00f6rfelden\u2010Walldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Escuriola Ettingshausen","sequence":"additional","affiliation":[{"name":"HZRM H\u00e4mophilie\u2010Zentrum Rhein Main Frankfurt\u2010M\u00f6rfelden M\u00f6rfelden\u2010Walldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Vdovin","sequence":"additional","affiliation":[{"name":"Izmaylovo Children's Hospital Haematological Centre Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Zozulya","sequence":"additional","affiliation":[{"name":"The State Haematological Scientific Centre RAMS Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Plyushch","sequence":"additional","affiliation":[{"name":"The State Haematological Scientific Centre RAMS Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Svirin","sequence":"additional","affiliation":[{"name":"Izmaylovo Children's Hospital Haematological Centre Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Andreeva","sequence":"additional","affiliation":[{"name":"St. Petersburg State Healthcare Institution St. Petersburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Bubansk\u00e1","sequence":"additional","affiliation":[{"name":"Children Faculty Hospital with Policlinic Bansk\u00e1 Bystrica Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Campos","sequence":"additional","affiliation":[{"name":"Centro Hospitalar Porto Hospital de Santo Ant\u00f3nio Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Benedik\u2010Dolni\u010dar","sequence":"additional","affiliation":[{"name":"Children's Hospital Oncology\u2010Hematology Unit University Medical Center Ljubljana Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Jim\u00e9nez\u2010Yuste","sequence":"additional","affiliation":[{"name":"Hospital La Paz Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Kitanovski","sequence":"additional","affiliation":[{"name":"Children's Hospital Oncology\u2010Hematology Unit University Medical Center Ljubljana Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Klukowska","sequence":"additional","affiliation":[{"name":"Medical Academy Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Momot","sequence":"additional","affiliation":[{"name":"Altai Hematological Center Altai Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Osmulskaya","sequence":"additional","affiliation":[{"name":"State Healthcare Institution of Omsk Region Omsk Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Prieto","sequence":"additional","affiliation":[{"name":"Hospital General Yag\u00fce Castilla Leon Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Z.","family":"\u0160alek","sequence":"additional","affiliation":[{"name":"University Hospital REBRO Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Velasco","sequence":"additional","affiliation":[{"name":"Hospital Reina Sof\u00eda C\u00f3rdoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Pavlova","sequence":"additional","affiliation":[{"name":"Institute of Experimental Haematology and Transfusion Medicine University Clinic Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Oldenburg","sequence":"additional","affiliation":[{"name":"Institute of Experimental Haematology and Transfusion Medicine University Clinic Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Knaub","sequence":"additional","affiliation":[{"name":"Octapharma AG Lachen Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Octapharma Pharmazeutika Produktionsges.mbH Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Belyanskaya","sequence":"additional","affiliation":[{"name":"Octapharma AG Lachen Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Walter","sequence":"additional","affiliation":[{"name":"Octapharma AG Lachen Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the ObsITI study group and the ObsITI committee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)90874-3"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.20162"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.1999.00368.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2009.02116.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1615621"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12672"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.1999.00311.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1423-0410.1996.tb01346.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.1999.00195.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.3.983.983"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.1995.tb00036.x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(77)90871-6"},{"key":"e_1_2_9_14_1","first-page":"339","article-title":"Successful immune tolerance therapy of FVIII\u2010inhibitors in children after changing\u00a0from high to intermediate purity FVIII\u00a0concentrate","volume":"72","author":"Kreuz W","year":"1996","journal-title":"Ann Hematol"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2007.01579.x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03615.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH12-07-0521"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12004"},{"key":"e_1_2_9_19_1","first-page":"16","article-title":"Immune tolerance induction (ITI) in haemophilia A \u2013 patients with inhibitors \u2013 the choice of concentrate affecting success","volume":"86","author":"Kreuz W","year":"2001","journal-title":"Haematologica"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.1996.tb00022.x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1653759"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-08-369132"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2006.01296.x"},{"key":"e_1_2_9_24_1","first-page":"1186","article-title":"Immune tolerance in hemophilia with factor VIII inhibitors: predictors of success","volume":"86","author":"Mariani G","year":"2001","journal-title":"Haematologica"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12050"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04493.x"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12263"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2007.01497.x"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2009.02122.x"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01880.x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12052"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhae.12774","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.12774","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hae.12774","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.12774","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T05:27:34Z","timestamp":1695533254000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.12774"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,23]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,1]]}},"alternative-id":["10.1111\/hae.12774"],"URL":"https:\/\/doi.org\/10.1111\/hae.12774","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,23]]}}}