{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T12:12:59Z","timestamp":1783599179282,"version":"3.55.0"},"reference-count":74,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008484","name":"BioMarin Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008484","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Gene therapy (GT) provides sustained FVIII levels without repeated infusions in Hemophilia A (HA) patients thus overcoming a major limitation of replacement therapy. However, issues remain e.g., patient selection criteria, duration and variability of transgene expression, quality of life and long\u2010term safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This expert opinion guidance aims to define the optimal operational pathway and organizational model in Italy for the approved gene therapy (GT) product valoctocogene roxaparvovec, for patients with HA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A multidisciplinary Working Group (healthcare professionals experienced in managing patients with HA and representatives of patients\u2019 Associations) critically analysed the Summary of Product Characteristics (SmPC) of valoctocogene roxaparvovec and some key publications concerning GT in haemophilia. The emerging evidence, alongside with the Working Group member expertise, helped to develop this journey for Italian patients with HA treated with this AAV5\u2010FVIII based GT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The present journey is divided into five sections: selection and screening of eligible patients, GT prescription, GT administration and post\u2010infusion (short\u2010term [\u22641 year] and long\u2010term [&gt;1 year\u2010up to 15 years] post\u2010GT follow\u2010up). Each phase involves collaboration between centres organized in a Hub and Spoke model, adoption of Shared Decision Making (SDM) approach, multidisciplinary team working and national data collection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This product\u2010specific operational pathway proposal provides Italian clinicians with a comprehensive framework for managing patients with HA treated with GT, acknowledging the evolving nature of this innovative therapy and the need for continuous evaluation of the proposed pathway. The present journey may need adaptation for other GT products.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hae.70332","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T07:36:32Z","timestamp":1781508992000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Italian Patients Journey for Gene Therapy in Haemophilia A"],"prefix":"10.1111","author":[{"given":"Giovanni","family":"Di Minno","sequence":"first","affiliation":[{"name":"Dipartimento Di Medicina Clinica e Chirurgia Federico II University, School of Medicine  Napoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaia","family":"Spadarella","sequence":"additional","affiliation":[{"name":"Dipartimento Di Scienze Biomediche Avanzate Federico II University, School of Medicine  Napoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Borchiellini","sequence":"additional","affiliation":[{"name":"Regional Centre For Hemorrhagic and Thrombotic Diseases Hematology Unit AOU Citt\u00e0 della Salute e della Scienza  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Borrelli","sequence":"additional","affiliation":[{"name":"Direzione Sanitaria AOU \u201cFederico II\u201d  Napoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Buzzi","sequence":"additional","affiliation":[{"name":"Fondazione Paracelso  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"Castaman","sequence":"additional","affiliation":[{"name":"Center For Bleeding Disorders and Coagulation Careggi University Hospital  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Cecchi","sequence":"additional","affiliation":[{"name":"UOC Farmacia ospedaliera Dell' Azienda Ospedaliero\u2010Universitaria Careggi  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raimondo","family":"De Cristofaro","sequence":"additional","affiliation":[{"name":"Dipartimento Di Medicina e Chirurgia Traslazionale Universit\u00e0 Cattolica S. Cuore  Rome Italy"},{"name":"Servizio Malattie Emorragiche e Trombotiche Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"La Mura","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa  Milan Italy"},{"name":"Department of Pathophysiology and Transplantation Universit\u00e0 Degli Studi di Milano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Lupi","sequence":"additional","affiliation":[{"name":"Federation of Haemophilia Associations (FedEmo)  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Malcangi","sequence":"additional","affiliation":[{"name":"UOSD Centro Emofilia e Trombosi Azienda Ospedaliero Universitaria Policlinico di Bari  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Elisa","family":"Mancuso","sequence":"additional","affiliation":[{"name":"Center For Thrombosis and Hemorrhagic Diseases IRCCS Humanitas Research Hospital  Milan Italy"},{"name":"Humanitas University, Pieve Emanuele  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Francesca","family":"Mansueto","sequence":"additional","affiliation":[{"name":"Dipartimento Di Oncologia, U.O. Ematologia Policlinico Paolo Giaccone  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Santoro","sequence":"additional","affiliation":[{"name":"Dipartimento Di Medicina Traslazionale e Di Precisione, Ematologia Sapienza Universit\u00e0 di Roma  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita Carlotta","family":"Santoro","sequence":"additional","affiliation":[{"name":"Hemostasis and Thrombosis Unit Azienda Ospedaliero Universitaria Dulbecco  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi Piero","family":"Solimeno","sequence":"additional","affiliation":[{"name":"Division of Orthopaedic Surgery and Traumatology Foundation IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annarita","family":"Tagliaferri","sequence":"additional","affiliation":[{"name":"Regional Reference Centre For Inherited Bleeding Disorders Parma University Hospital  Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezio","family":"Zanon","sequence":"additional","affiliation":[{"name":"Centro Regionale HUB Multidisciplinare Per La prevenzione, Profilassi e Trattamento\u00a0Avanzato Dell'artropatia emofilica. Clinica Medica 1\u00b0 Ad Indirizzo Trombotico\u2010Emorragico Azienda Ospedale Universit\u00e0 Di Padova  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Garagiola","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"Peyvandi","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa  Milan Italy"},{"name":"Department of Pathophysiology and Transplantation Universit\u00e0 Degli Studi di Milano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"issue":"1","key":"e_1_2_12_2_1","first-page":"58","article-title":"New Data From the Italian National Register of Congenital Coagulopathies, 2016 Annual Survey","volume":"18","author":"Abbonizio F.","year":"2020","journal-title":"Blood Transfusion"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12672"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.221093"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2022.2002842"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14046"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538\u20107836.2008.03270.x"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200106073442307"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010021\u201000278\u2010x"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/17474086.2018.1486704"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14313"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(15)01123\u2010X"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14709"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(20)32722\u20107"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1516437"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/2040620712464509"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2018.08.003"},{"issue":"3","key":"e_1_2_12_18_1","first-page":"223","article-title":"Emicizumab for the Treatment of Haemophilia A: A Narrative Review","volume":"17","author":"Franchini M.","year":"2019","journal-title":"Blood Transfusion"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231810228"},{"key":"e_1_2_12_20_1","unstructured":"Agency EM. EPAR Altuvoct. [cited 2025 April 29];https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/altuvoct\u2010epar\u2010product\u2010information_en.pdf."},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2209226"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13816"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/hematology.2019000007"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102018\u201007\u2010820720"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.2147\/PPA.S355627"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rpth.2024.102615"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2113708"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.15071"},{"key":"e_1_2_12_29_1","unstructured":"European Medicines Agency. EPAR Roctavian. [cited 2025 November 11];https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/roctavian\u2010epar\u2010product\u2010information_en.pdf."},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.15125"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.70113"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.18553\/jmcp.2021.27.3.316"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2022.101011"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13088"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14425"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0224899"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1177\/20406207221145627"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transci.2019.08.011"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13972"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2211075"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14546"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14440"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14420"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.11.014"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14545"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14608"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2020.100737"},{"issue":"3","key":"e_1_2_12_48_1","first-page":"196","article-title":"Gene Therapy of Hemophilia: Recommendations from the German, Austrian, and Swiss Society for Thrombosis and Haemostasis Research (GTH)","volume":"43","author":"Miesbach W.","year":"2023","journal-title":"Hamostaseologie"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.2147\/JBM.S371438"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14516"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.farma.2023.01.003"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.2478\/jhp\u20102022\u20100003"},{"key":"e_1_2_12_53_1","unstructured":"EAHAD\u2010EHC.Joint Statement on Promoting Hub\u2010and\u2010Spoke Model for the Treatment of Haemophilia and Rare Bleeding Disorders Using Gene Therapies[cited 2023 October 2];https:\/\/www.ehc.eu\/wp\u2010content\/uploads\/EHC\u2010EAHAD\u2010Position\u2010Statement\u2010on\u2010GT.pdf."},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2023.101118"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.2147\/PPA.S406894"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.15025"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtha.2026.02.026"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023010723"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtha.2024.08.018"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1358"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtha.2023.12.005"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2024013750"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010022\u201001751\u20100"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1908490"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjsurg.2018.01.011"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14015"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtha.2023.12.018"},{"key":"e_1_2_12_68_1","unstructured":"AIFA.Monitoring Registers[cited 2023 October 2];https:\/\/aifa.gov.it\/registri\u2010farmaci\u2010sottoposti\u2010a\u2010monitoraggio."},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14985"},{"key":"e_1_2_12_70_1","unstructured":"World Federation of Hemophilia.Gene Therapy Registry[cited 2023 October 2];https:\/\/wfh.org\/research\u2010and\u2010data\u2010collection\/gene\u2010therapy\u2010registry\/."},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2009.182"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2021.287"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2021.05.012"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3742"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-59403-9"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.70332","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hae.70332","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.70332","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T11:13:12Z","timestamp":1783595592000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.70332"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,15]]},"references-count":74,"alternative-id":["10.1111\/hae.70332"],"URL":"https:\/\/doi.org\/10.1111\/hae.70332","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,15]]},"assertion":[{"value":"2025-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"hae.70332"}}