{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T10:34:49Z","timestamp":1788863689044,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T00:00:00Z","timestamp":1695168000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Turoctocog alfa pegol (N8\u2010GP) is a glycoPEGylated, extended half\u2010life (EHL), human recombinant factor VIII (FVIII) approved for the treatment and prevention of bleeding episodes in patients with haemophilia A. Since its launch in August 2019,\u00a0&gt;\u00a0800 patients have been treated worldwide.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To present data from identified post\u2010marketing cases of less\u2010than\u2010expected FVIII activity in previously treated patients (PTPs) without inhibitors after switching to N8\u2010GP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The post\u2010marketing safety database was searched using keywords such as \u2018coagulation FVIII level decreased\u2019. Identified cases reported prior to 13 October 2021 were included in this report. Cases in which patients had FVIII inhibitors were excluded.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here we report 14 cases of less\u2010than\u2010expected FVIII activity. Details varied greatly amongst the cases. At presentation, FVIII activity ranged from 1% (15 min post\u2010dose) to 51% (2 days post\u2010dose). Seven patients experienced bleeding episodes after switching to N8\u2010GP with heterogeneity in bleeding presentations. Six out of seven patients who were tested for anti\u2010PEG IgG and\/or IgM antibodies were positive. In all known cases, FVIII activity returned to the expected range when switched to an alternative FVIII replacement product.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In conclusion, the 14 reported cases of less\u2010than\u2010expected FVIII activity, without presence of detectable FVIII inhibitors, presented with heterogenous characteristics, and wide variations in FVIII activity and anti\u2010PEG antibody titre. FVIII activity returned to the expected range after switching to alternative FVIII products. In line with WFH guidelines, monitoring of FVIII activity can ensure FVIII activity in the expected range. The safety surveillance of N8\u2010GP continues.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.14864","type":"journal-article","created":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T18:08:41Z","timestamp":1695233321000},"page":"1475-1482","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cases of less\u2010than\u2010expected FVIII activity in previously treated patients during post\u2010marketing surveillance of N8\u2010GP"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1585-4100","authenticated-orcid":false,"given":"Johannes","family":"Oldenburg","sequence":"first","affiliation":[{"name":"Institute for Experimental Haematology and Transfusion Medicine University of Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4269-8713","authenticated-orcid":false,"given":"Gary","family":"Benson","sequence":"additional","affiliation":[{"name":"Department of Haematology Belfast City Hospital  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0135-1051","authenticated-orcid":false,"given":"Pratima","family":"Chowdary","sequence":"additional","affiliation":[{"name":"Katharine Dormandy Haemophilia and Thrombosis Centre Royal Free Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8596-9870","authenticated-orcid":false,"given":"Susan","family":"Halimeh","sequence":"additional","affiliation":[{"name":"Rhine Ruhr Coagulation Centre  Duisburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Nagoya University Hospital Department of Transfusion Medicine Nagoya University Hospital  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"N\u00f8rland","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S  S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd Nawi","family":"Wahid","sequence":"additional","affiliation":[{"name":"Novo Nordisk Health Care AG  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laszlo","family":"Nemes","sequence":"additional","affiliation":[{"name":"DepartmentMedical Center of the Hungarian Defence Forces National Hemophilia Center and Hemostasis  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/rth2.12220"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH16-06-0444"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13246"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15036"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12161"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14959"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/rth2.12674"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14958"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH17-03-0166"},{"key":"e_1_2_11_11_1","unstructured":"FDA. ImmunogenicityTesting of Therapeutic Protein Products \u2014 Developing and Validating Assays for Anti\u2010Drug Antibody Detection (Guidance for Industry).2019."},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2004.06.002"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2008.09.020"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.6b03437"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022007529"},{"key":"e_1_2_11_16_1","unstructured":"PezeshkpoorB SeredaN BerkemeierAC et\u00a0al.Development of Anti\u2010drug inhibitory antibodies against PEG after treatment with PEGylated FVIII therapeutic."},{"key":"e_1_2_11_17_1","first-page":"1","article-title":"Clinical relevance of pre\u2010existing and treatment\u2010induced anti\u2010poly(ethylene glycol) antibodies","author":"Freire Haddad H","year":"2021","journal-title":"Regen Eng Transl Med"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.6b03109"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022008989"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.2c04543"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.1c05922"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-016-1961-x"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.6.1836"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2012.02854.x"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.2491\/jjsth.32.330"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-142816"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000694"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15395"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13963"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14294"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14046"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.14864","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T11:20:15Z","timestamp":1705663215000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.14864"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,20]]},"references-count":30,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1111\/hae.14864"],"URL":"https:\/\/doi.org\/10.1111\/hae.14864","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,20]]},"assertion":[{"value":"2023-02-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}