Inhibitor development upon switching from plasma-derived to recombinant factor VIII in previously untreated patients with severe hemophilia A: the PUP-SWITCH study

Background: The SIPPET randomized clinical trial showed that in previously untreated patients (PUPs) with severe hemophilia A, treatment with plasma-derived factor (F)VIII (pdFVIII) within the first 50 exposure days (EDs) was associated with a lower cumulative incidence of inhibitors than with recom...

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Main Authors: Syna Miri, Frits R. Rosendaal, Kaan Kavakli, Peyman Eshghi, Soha Mohammadi Moghaddam, Sara Scardo, Behnaz Habibpanah, Mohsen Elalfy, Susan Halimeh, Gabriella Nicolò, Dilek Gökçebay, Namık Özbek, Tiraje Celkan, Ahmad Mohammadi, Mehran Karimi, Amin Shahsavani, Bariş Yılmaz, Canan Albayrak, Burcak Gunes, Zühre Kaya, Yilmaz Ay, Sinan Akbayram, Nazan Sarper, Pier Mannuccio Mannucci, Flora Peyvandi
Format: Article
Language:English
Published: Elsevier 2024-11-01
Series:Research and Practice in Thrombosis and Haemostasis
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Online Access:http://www.sciencedirect.com/science/article/pii/S2475037924002905
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author Syna Miri
Frits R. Rosendaal
Kaan Kavakli
Peyman Eshghi
Soha Mohammadi Moghaddam
Sara Scardo
Behnaz Habibpanah
Mohsen Elalfy
Susan Halimeh
Gabriella Nicolò
Dilek Gökçebay
Namık Özbek
Tiraje Celkan
Ahmad Mohammadi
Mehran Karimi
Amin Shahsavani
Bariş Yılmaz
Canan Albayrak
Burcak Gunes
Zühre Kaya
Yilmaz Ay
Sinan Akbayram
Nazan Sarper
Pier Mannuccio Mannucci
Flora Peyvandi
author_facet Syna Miri
Frits R. Rosendaal
Kaan Kavakli
Peyman Eshghi
Soha Mohammadi Moghaddam
Sara Scardo
Behnaz Habibpanah
Mohsen Elalfy
Susan Halimeh
Gabriella Nicolò
Dilek Gökçebay
Namık Özbek
Tiraje Celkan
Ahmad Mohammadi
Mehran Karimi
Amin Shahsavani
Bariş Yılmaz
Canan Albayrak
Burcak Gunes
Zühre Kaya
Yilmaz Ay
Sinan Akbayram
Nazan Sarper
Pier Mannuccio Mannucci
Flora Peyvandi
author_sort Syna Miri
collection DOAJ
description Background: The SIPPET randomized clinical trial showed that in previously untreated patients (PUPs) with severe hemophilia A, treatment with plasma-derived factor (F)VIII (pdFVIII) within the first 50 exposure days (EDs) was associated with a lower cumulative incidence of inhibitors than with recombinant FVIII (rFVIII). Switching to rFVIII beyond 50 EDs with pdFVIII is a treatment often implemented by many centers. The question is whether or not this switch may induce a risk of inhibitor development. Objectives: We investigated if in PUPs with severe hemophilia A switched after 50 EDs from pdFVIII to rFVIII, a novel inhibitor peak appears. Methods: The PUP-SWITCH observational retrospective study was designed to investigate the cumulative incidence of novel inhibitors after switching PUPs to rFVIII after 50 and before 150 EDs. Hemophilia centers that routinely switched PUPs from pdFVIII to rFVIII within this exposure time frame were invited to participate. Patients were followed up for at least 50 EDs after the switch. Results: Ninety-seven patients were evaluated, and 87 were included according to eligibility criteria between 2020 and 2022. Only one of them developed an inhibitor 20 EDs after switching, so the cumulative incidence was 1.15% (95% CI, 0.03%-6.24%). Conclusion: PUP-SWITCH, a study focusing on PUPs undergoing a product class switch from pdFVIII to rFVIII after 50 EDs, showed that switching appears to be safe pertaining to the risk of development of new inhibitors.
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spelling doaj-art-4b03b64b310440f8a91a94aeb97af98c2025-08-20T02:40:07ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792024-11-018810259510.1016/j.rpth.2024.102595Inhibitor development upon switching from plasma-derived to recombinant factor VIII in previously untreated patients with severe hemophilia A: the PUP-SWITCH studySyna Miri0Frits R. Rosendaal1Kaan Kavakli2Peyman Eshghi3Soha Mohammadi Moghaddam4Sara Scardo5Behnaz Habibpanah6Mohsen Elalfy7Susan Halimeh8Gabriella Nicolò9Dilek Gökçebay10Namık Özbek11Tiraje Celkan12Ahmad Mohammadi13Mehran Karimi14Amin Shahsavani15Bariş Yılmaz16Canan Albayrak17Burcak Gunes18Zühre Kaya19Yilmaz Ay20Sinan Akbayram21Nazan Sarper22Pier Mannuccio Mannucci23Flora Peyvandi24Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, the NetherlandsEge Hemophilia Center, Pediatric Congenital Hematologic Disorders Research Center, Izmir, TürkiyePediatric Congenital Hematologic Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranPediatric Congenital Hematologic Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranAngelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, ItalyPediatric Congenital Hematologic Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Pediatric Hematology/Oncology, Ain Shams University, Cairo, EgyptCoagulation and Thrombosis Centre, Gerinnungszentrum Rhein Ruhr, Duisburg, GermanyDepartment of Healthcare Professions, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Pediatric Hematology/Oncology and Pediatric Bone Marrow Transplantation Unit, Ankara Bilkent City Hospital, Ankara, TürkiyeDepartment of Pediatric Hematology/Oncology and Pediatric Bone Marrow Transplantation Unit, Ankara Bilkent City Hospital, Ankara, TürkiyeDepartment of Pediatric Hematology and Oncology, Cerrahpaşa Faculty of Medicine, İstanbul University, Istanbul, TürkiyeEsfahan Hemophilia Treatment Centre, Seyed Shohada Hospital, Esfahan, IranPediatric Hematology-Oncology Department, American Hospital Dubai, Dubai, United Arab Emirates; Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, IranHematology Research Center, Shiraz University of Medical Sciences, Shiraz, IranDepartment of Pediatric Health and Diseases, Marmara University, Istanbul, TürkiyeDepartment of Pediatric Hematology and Oncology BMT Unit, Ondokuz Mayıs University Faculty of Medicine, Samsun, Türkiyeİzmir Tepecik Training and Research Hospital, Clinic of Pediatric Hematology, İzmir, TürkiyeDepartment of Pediatric Hematology, Gazi University Faculty of Medicine, Ankara, TürkiyeDepartment of Pediatric Hematology, Pamukkale University Faculty of Medicine, Denizli, TürkiyeDepartment of Pediatric Hematology and Oncology BMT Unit, Gaziantep University Faculty of Medicine, Gaziantep, TürkiyeDepartment of Pediatric Hematology, Kocaeli University School of Medicine, Kocaeli, TürkiyeAngelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, ItalyAngelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy; Correspondence Flora Peyvandi, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via Pace 9, Milan 20122, Italy.Background: The SIPPET randomized clinical trial showed that in previously untreated patients (PUPs) with severe hemophilia A, treatment with plasma-derived factor (F)VIII (pdFVIII) within the first 50 exposure days (EDs) was associated with a lower cumulative incidence of inhibitors than with recombinant FVIII (rFVIII). Switching to rFVIII beyond 50 EDs with pdFVIII is a treatment often implemented by many centers. The question is whether or not this switch may induce a risk of inhibitor development. Objectives: We investigated if in PUPs with severe hemophilia A switched after 50 EDs from pdFVIII to rFVIII, a novel inhibitor peak appears. Methods: The PUP-SWITCH observational retrospective study was designed to investigate the cumulative incidence of novel inhibitors after switching PUPs to rFVIII after 50 and before 150 EDs. Hemophilia centers that routinely switched PUPs from pdFVIII to rFVIII within this exposure time frame were invited to participate. Patients were followed up for at least 50 EDs after the switch. Results: Ninety-seven patients were evaluated, and 87 were included according to eligibility criteria between 2020 and 2022. Only one of them developed an inhibitor 20 EDs after switching, so the cumulative incidence was 1.15% (95% CI, 0.03%-6.24%). Conclusion: PUP-SWITCH, a study focusing on PUPs undergoing a product class switch from pdFVIII to rFVIII after 50 EDs, showed that switching appears to be safe pertaining to the risk of development of new inhibitors.http://www.sciencedirect.com/science/article/pii/S2475037924002905factor VIIIfactor VIII/adverse eventsfactor VIII/immunologyfactor VIII/therapeutic usehemophilia A/drug therapy
spellingShingle Syna Miri
Frits R. Rosendaal
Kaan Kavakli
Peyman Eshghi
Soha Mohammadi Moghaddam
Sara Scardo
Behnaz Habibpanah
Mohsen Elalfy
Susan Halimeh
Gabriella Nicolò
Dilek Gökçebay
Namık Özbek
Tiraje Celkan
Ahmad Mohammadi
Mehran Karimi
Amin Shahsavani
Bariş Yılmaz
Canan Albayrak
Burcak Gunes
Zühre Kaya
Yilmaz Ay
Sinan Akbayram
Nazan Sarper
Pier Mannuccio Mannucci
Flora Peyvandi
Inhibitor development upon switching from plasma-derived to recombinant factor VIII in previously untreated patients with severe hemophilia A: the PUP-SWITCH study
Research and Practice in Thrombosis and Haemostasis
factor VIII
factor VIII/adverse events
factor VIII/immunology
factor VIII/therapeutic use
hemophilia A/drug therapy
title Inhibitor development upon switching from plasma-derived to recombinant factor VIII in previously untreated patients with severe hemophilia A: the PUP-SWITCH study
title_full Inhibitor development upon switching from plasma-derived to recombinant factor VIII in previously untreated patients with severe hemophilia A: the PUP-SWITCH study
title_fullStr Inhibitor development upon switching from plasma-derived to recombinant factor VIII in previously untreated patients with severe hemophilia A: the PUP-SWITCH study
title_full_unstemmed Inhibitor development upon switching from plasma-derived to recombinant factor VIII in previously untreated patients with severe hemophilia A: the PUP-SWITCH study
title_short Inhibitor development upon switching from plasma-derived to recombinant factor VIII in previously untreated patients with severe hemophilia A: the PUP-SWITCH study
title_sort inhibitor development upon switching from plasma derived to recombinant factor viii in previously untreated patients with severe hemophilia a the pup switch study
topic factor VIII
factor VIII/adverse events
factor VIII/immunology
factor VIII/therapeutic use
hemophilia A/drug therapy
url http://www.sciencedirect.com/science/article/pii/S2475037924002905
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