{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T17:25:14Z","timestamp":1783445114276,"version":"3.54.6"},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,10,17]],"date-time":"2017-10-17T00:00:00Z","timestamp":1508198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007343","name":"Shire","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007343","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009431","name":"Baxalta","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","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\/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":[[2018,1]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Outcome data on treatment of patients with haemophilia A spanning several years of real\u2010world evidence collection are currently very limited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim and methods<\/jats:title><jats:p>The global prospective long\u2010term Advate<jats:sup>\u00ae<\/jats:sup> Haemophilia A Outcome Database (<jats:styled-content style=\"fixed-case\">AHEAD<\/jats:styled-content>) cohort study collects real\u2010world data from patients with severe and moderate haemophilia. We report an interim data read\u2010out after three\u00a0years of observation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 522 patients were enrolled from 21 countries: 334 completed year 1 follow\u2010up, 238 completed year 2 and 136 completed year 3, with an overall follow\u2010up of 811 patient\u2010years. Median annual bleeding rates (<jats:styled-content style=\"fixed-case\">ABR<\/jats:styled-content>) were 1.7 in the prophylaxis group and 8.9 in the on\u2010demand group at year 1 visit, 1.6 and 13.0, respectively, at year 2 visit and 2.2 and 10.3, respectively, at year 3 visit. Moreover, about 42% of patients on prophylaxis vs 12% of patients on on\u2010demand had zero annual joint bleeding rates (<jats:styled-content style=\"fixed-case\">AJBR<\/jats:styled-content>). Effectiveness of prophylaxis and on\u2010demand treatment was deemed excellent\/good in the majority of cases. Octocog alfa (Advate<jats:sup>\u00ae<\/jats:sup>) was well tolerated. The inhibitors that developed in nine patients all disappeared spontaneously. Three patients had been previously exposed to <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> for \u226450 exposure days (<jats:styled-content style=\"fixed-case\">ED<\/jats:styled-content>s), 3 for &gt;50 <jats:styled-content style=\"fixed-case\">ED<\/jats:styled-content>s and 3 showed a borderline positive inhibitory activity (\u22640.6\u00a0<jats:styled-content style=\"fixed-case\">BU<\/jats:styled-content>\/mL).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data confirm that the goal of zero bleeds is achievable, although not yet achieved in all patients. Understanding reasons behind the lower response to standard prophylaxis regimens in some patients and personalizing prophylactic treatment may further improve outcome in patients with haemophilia A.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.13361","type":"journal-article","created":{"date-parts":[[2017,10,17]],"date-time":"2017-10-17T14:19:27Z","timestamp":1508249967000},"page":"85-96","source":"Crossref","is-referenced-by-count":39,"title":["Pattern of bleeding in a large prospective cohort of haemophilia A patients: A three\u2010year follow\u2010up of the <scp>AHEAD<\/scp> (Advate in HaEmophilia A outcome Database) study"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2001-5958","authenticated-orcid":false,"given":"K.","family":"Khair","sequence":"first","affiliation":[{"name":"Haemophilia Comprehensive Care Centre Great Ormond Street Hospital for Children NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. G.","family":"Mazzucconi","sequence":"additional","affiliation":[{"name":"Universita\u2019 Roma La Sapienza  Policlinico Umberto I Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Parra","sequence":"additional","affiliation":[{"name":"Unidad de Hemofilia\u2010Banc de Sang i Teixits Hospital Universitari Vall d'Hebron  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Santagostino","sequence":"additional","affiliation":[{"name":"Angelo Bianchi Bonomi Haemophilia and Thrombosis Centre IRCCS Fondazione Ca\u2019 Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. A.","family":"Tsakiris","sequence":"additional","affiliation":[{"name":"Diagnostic Hematology University Hospital  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Hermans","sequence":"additional","affiliation":[{"name":"Haemophilia Clinic Division of Haematology St\u2010Luc University Hospital  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3038-2145","authenticated-orcid":false,"given":"J.","family":"Oldenburg","sequence":"additional","affiliation":[{"name":"Institute for Experimental Hematology and Transfusion Medicine Bonn University Clinic  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Spotts","sequence":"additional","affiliation":[{"name":"Shire  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Steinitz\u2010Trost","sequence":"additional","affiliation":[{"name":"Shire  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Gringeri","sequence":"additional","affiliation":[{"name":"Shire  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,10,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13405-8"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2006.01268.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1538-7836.2003.00262.x"},{"key":"e_1_2_8_5_1","unstructured":"Report of a joint WHO\/WFH\/ISTH meeting. 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