{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T12:30:53Z","timestamp":1791549053076,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","issue":"S3","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Over the last decades progress in haemophilia treatment has been remarkable and prophylaxis with clotting factor concentrates in haemophilia A and B has been established as the standard of care in individuals with haemophilia and a severe bleeding phenotype. Besides clotting factor products with prolonged half\u2010life non\u2010factor therapies were developed which enable prophylaxis via subcutaneous administration. Factor VIIIa mimetics like emicizumab facilitate the coagulation pathway and are used in routine clinical practice for indivdiduals with haemophilia A. Rebalancing therapeutic agents like fitusiran, concizumab, marstacimab and serpin PC block the anticoagulant pathway and clinical trials using these products in individuals with haemophilia A and B are ongoing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim and Methods<\/jats:title><jats:p>A narrative review to asess the benefits and risks of non\u2010factor therapies taking in to account re\u2010defined haemophilia treatment goals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Prophylaxis for prevention of bleeds using non\u2010factor products by subcutaneous administration is effective and results in reductions of bleeding episodes in individuals with haemophilia A or B with and without inhibitors. The treatment with emicizumab showed tolerable safety both in clinical trials and long\u2010term real\u2010world observations with few thrombotic events. In some clinical trials with rebalancing therapies (fitusiran and concizumab) thrombotic events occurred. Monitoring of the haemostatic function of novel therapies especially with concomitant haemostatic treatment is not yet established.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>With the advent of novel therapeutic agents including factor concentrates with ultra\u2010long half\u2010life and improved FVIIIa mimetics aimed at raising the bar of protection into the non\u2010hemophilic range redefinition of haemophilia treatment goals is eagerly needed.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.14976","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T06:21:40Z","timestamp":1710397300000},"page":"39-44","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Benefits and risks of non\u2010factor therapies: Redefining haemophilia treatment goals in the era of new technologies"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7113-4028","authenticated-orcid":false,"given":"Maria Elisa","family":"Mancuso","sequence":"first","affiliation":[{"name":"Center for Thrombosis and Hemorrhagic Diseases IRCCS Humanitas Research Hospital, Rozzano  Milan Italy"},{"name":"Humanitas University, Pieve Emanuele  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6112-6166","authenticated-orcid":false,"given":"Stacy E.","family":"Croteau","sequence":"additional","affiliation":[{"name":"Boston Children's Hospital, Boston Hemophilia Center Harvard Medical School  Boston USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4194-8183","authenticated-orcid":false,"given":"Robert","family":"Klamroth","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Hemophilia Treatment Center Vivantes Klinikum im Friedrichshain  Berlin Germany"},{"name":"Institute of Experimental Hematology and Transfusion Medicine University Hospital Bonn Medical Faculty University of Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14046"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2021.100890"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32722-7"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019001869"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1703068"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1803550"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rpth.2023.102181"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtha.2023.09.034"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057479"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15682"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020010331"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-021-01042-w"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023021832"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009217"},{"key":"e_1_2_11_16_1","article-title":"FRONTIER1: a phase 1\/2 dose escalation study of a novel factor VIIIa mimetic bispecific antibody, mim8, for evaluation of safety, pharmacokinetics, and efficacy [abstract]","author":"Chowdary PJF","journal-title":"ISTH"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14884"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtha.2022.12.023"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0271330"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.29074\/ascls.2019002204"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14679"},{"key":"e_1_2_11_22_1","unstructured":"HEMLIBRA\u00ae (emicizumab\u2010kxwh) [package insert].Genentech Inc. 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