{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:23:57Z","timestamp":1790634237435,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T00:00:00Z","timestamp":1687132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["pericles.pericles-gcp.literatumonline.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The NuProtect study reported data on the immunogenicity, efficacy and tolerability of simoctocog alfa (Nuwiq<jats:sup>\u00ae<\/jats:sup>) in 108 previously untreated patients with severe haemophilia A planned to be treated for \u2265100 exposure days or up to 5\u00a0years. The NuProtect\u2010Extension study collected long\u2010term prophylaxis data in children with severe haemophilia A.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients who completed the NuProtect study according to the protocol were eligible for the NuProtect\u2010Extension study, a prospective, multinational, non\u2010controlled, Phase 3b study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 48 patients who entered the extension study, 47 (median age 2.8\u00a0years) received prophylaxis with simoctocog alfa for a median of 24\u00a0months, with 82%\u201388% on a twice\u2010weekly or less regimen. No patient developed FVIII inhibitors during the extension study. The median (IQR) annualized bleeding rate (ABR) during prophylaxis was 0 (0\u20130.5) for spontaneous bleeding episodes (BEs) and 1.00 (0\u20131.95) for all BEs. ABRs estimated using a negative binomial model were .28 (95% CI: .15, .53) for spontaneous and 1.62 (95% CI: 1.09, 2.42) for all BEs. During the median follow\u2010up of 24\u00a0months, 34 (72%) patients had zero spontaneous BEs and 46 (98%) had zero spontaneous joint BEs. Efficacy in treating BEs was excellent or good for 78.2% of rated BEs, and efficacy of surgical prophylaxis was excellent for two rated surgeries. No treatment\u2010related adverse events were reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>No FVIII inhibitors developed during long\u2010term prophylaxis in the NuProtect\u2010Extension study. Prophylaxis with simoctocog alfa was efficacious and well\u2010tolerated, and is therefore an attractive long\u2010term option for children with severe haemophilia A.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.14796","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T15:18:41Z","timestamp":1687187921000},"page":"1005-1012","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Long\u2010term immunogenicity, efficacy and tolerability of simoctocog alfa in patients with severe haemophilia A who had completed the NuProtect study in previously untreated patients"],"prefix":"10.1111","volume":"29","author":[{"given":"Mary","family":"Mathias","sequence":"first","affiliation":[{"name":"Haemophilia Comprehensive Care Centre Great Ormond Street Hospital for Children NHS Foundation Trust NIHR GOSH BRC London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Abashidze","sequence":"additional","affiliation":[{"name":"JSC Institute of Haematology and Transfusiology Tbilisi Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aby","family":"Abraham","sequence":"additional","affiliation":[{"name":"Department of Hematology Christian Medical College Vellore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Belletrutti","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Hematology\/Oncology\/BMT University of British Columbia and British Columbia Children's Hospital Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5350-1763","authenticated-orcid":false,"given":"Manuel","family":"Carcao","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Division of Haematology\/Oncology and Child Health Evaluative Sciences Research Institute Hospital for Sick Children Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Chambost","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology Oncology Children Hospital La Timone APHM and Inserm, UMR 1062 Aix Marseille University Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony K. C.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics McMaster Centre of Transfusion Research McMaster University Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonid","family":"Dubey","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Western Ukrainian Specialized Children's Medical Centre Lviv Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Ducore","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of California Davis Medical Center Sacramento USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Lambert","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence pour le Traitement des H\u00e9mophiles H\u00f4pital Universitaire Bic\u00eatre APHP Le Kremlin Bic\u00eatre France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalya","family":"Kavardakova","sequence":"additional","affiliation":[{"name":"National Children's Specialized Clinic \u201cOHMATDET\u201d Kiev Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil","family":"Lohade","sequence":"additional","affiliation":[{"name":"Department of Hematology Sahyadri Speciality Hospital Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin","family":"Turea","sequence":"additional","affiliation":[{"name":"Scientific Research Institute of Mother and Child Health Care Chi\u015fin\u0103u Moldova"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John K. 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