{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T01:18:36Z","timestamp":1782436716036,"version":"3.54.5"},"reference-count":49,"publisher":"Georg Thieme Verlag KG","issue":"01","license":[{"start":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T00:00:00Z","timestamp":1673308800000},"content-version":"vor","delay-in-days":9,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bayer"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:p>\n            Introduction\u2003BAY 81\u20138973, a full-length recombinant factor VIII for hemophilia A treatment, has been extensively evaluated in previously treated patients in the LEOPOLD (Long-Term Efficacy Open-Label Program in Severe Hemophilia A Disease) clinical trials.<\/jats:p><jats:p>\n            Aim\u2003To assess BAY 81\u20138973 efficacy and safety when used for bleed prophylaxis and treatment in previously untreated\/minimally treated patients (PUPs\/MTPs).<\/jats:p><jats:p>\n            Methods\u2003In this phase III, multicenter, open-label, uncontrolled study, PUPs\/MTPs (&lt;6 years old) with severe hemophilia A received BAY 81\u20138973 (15\u201350\u2009IU\/kg) at least once weekly as prophylaxis. Primary efficacy endpoint was the annualized bleeding rate (ABR) within 48\u2009hours after prophylaxis infusion. Adverse events and immunogenicity were assessed. Patients who developed inhibitors were offered immune tolerance induction (ITI) treatment in an optional extension phase.<\/jats:p><jats:p>\n            Results\u2003Fifty-two patients were enrolled, with 43 patients (mean age: 13.6 months) treated. Median (interquartile range) ABR for all bleeds within 48\u2009hours of prophylaxis infusion was 0.0 (0.0\u20131.8) among patients without inhibitors (n\u2009=\u200920) and 0.0 (0.0\u20132.2) among all patients. As expected, inhibitors were the most frequent treatment-related adverse event (high titer: 17 [39.5%] patients; low titer: 6 [13.9%] patients). Six of 12 patients who underwent ITI treatment in the extension phase (high titer [n\u2009=\u20095], low titer [n\u2009=\u20091]) achieved a negative inhibitor titer.<\/jats:p><jats:p>\n            Conclusion\u2003BAY 81\u20138973 was effective for bleed prevention and treatment in PUPs\/MTPs. The observed inhibitor rate was strongly influenced by a cluster of inhibitor cases, and consequently, slightly higher than in other PUP\/MTP studies. Overall, the BAY 81\u20138973 benefit\u2013risk profile remains unchanged and supported by ongoing safety surveillance. Immune tolerance can be achieved with BAY 81\u20138973.<\/jats:p>","DOI":"10.1055\/s-0042-1757876","type":"journal-article","created":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T23:31:50Z","timestamp":1673393510000},"page":"027-039","source":"Crossref","is-referenced-by-count":7,"title":["BAY 81-8973 Efficacy and Safety in Previously Untreated and Minimally Treated Children with Severe Hemophilia A: The LEOPOLD Kids Trial"],"prefix":"10.1055","volume":"123","author":[{"given":"Rolf","family":"Ljung","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund-Pediatrics, Lund University, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony K. 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7113-4028","authenticated-orcid":false,"given":"Maria Elisa","family":"Mancuso","sequence":"additional","affiliation":[{"name":"Center for Thrombosis and Hemorrhagic Diseases, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonata","family":"Saulyte-Trakymiene","sequence":"additional","affiliation":[{"name":"Clinic of Children's Diseases, Faculty of Medicine, Vilnius University Hospital Santaros Klinikos, Vilnius University, Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gili","family":"Kenet","sequence":"additional","affiliation":[{"name":"Sheba Medical Center, The Israeli National Hemophilia Center, The Amalia Biron Thrombosis Research Institute and The Sackler Medical School, Tel Aviv University, Tel-Hashomer, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2023,1,10]]},"reference":[{"key":"ref1","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":"A Srivastava","year":"2020","journal-title":"Haemophilia"},{"issue":"09","key":"ref2","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1111\/j.1538-7836.2010.03962.x","article-title":"Blood-induced joint disease: the pathophysiology of hemophilic arthropathy","volume":"8","author":"L A Valentino","year":"2010","journal-title":"J Thromb Haemost"},{"issue":"01","key":"ref3","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/j.1365-2796.1992.tb00546.x","article-title":"Twenty-five years' experience of prophylactic treatment in severe haemophilia A and B","volume":"232","author":"I M Nilsson","year":"1992","journal-title":"J Intern 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