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    Oral Communication

    Hemophilia and Rare Bleeding Disorders

    Hemophilia Clinical - Inhibitors

    OC 50.3 - Inhibitor development upon switch after 50 EDs from plasma-derived to recombinant FVIII in PUPs with severe haemophilia A: the PUP-SWITCH study results

    Tuesday, June 27, 2023
    11:15 – 11:30 ET
    Room: 516
    Session Available As: Live-Stream and On-Demand

      Presenting Author(s)

    • Syna Miri, MSc

      PhD candidate
      Università degli Studi di Milano, Department of Biomedical Sciences for Health, Milan, Italy
      Milan, Lombardia, Italy

      • Co-Author(s)

    • FR

      Frits R. R. Rosendaal

      Professor
      Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
      Leiden, Zuid-Holland, Netherlands

    • KK

      Kaan Kavakli

      Professor
      Ege Hemophilia Center, Izmir, Turkey
      Izmir, Izmir, Turkey

    • PE

      Peyman Eshghi, MD

      Professor
      Pediatric Congenital Hematologic Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
      Tehran, Tehran, Iran

    • SM

      Soha Mohammadi Moghaddam

      MD
      Pediatric Congenital Hematologic Disorders Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
      Tehran, Tehran, Iran

    • ME

      Mohsen Elalfy

      Professor
      Ain Shams University, Cairo, Egypt
      Cairo, Al Qahirah, Egypt

    • Susan Halimeh

      Direktor
      Gerinnungszentrum Rhein-Ruhr
      Duisburg, Nordrhein-Westfalen, Germany

    • DG

      Dilek Gürlek Gökçebay

      Professor
      Ministry of Health Ankara City Hospital, Ankara, Turkey
      Ankara, Ankara, Turkey

    • N

      Namık Özbek

      Professor
      Ministry of Health Ankara City Hospital, Ankara, Turkey
      Ankara, Ankara, Turkey

    • TC

      Tiraje Celkan

      Professor
      Cerrahpaşa Faculty of Medicine, İstanbul University, Istanbul, Turkey
      Istanbul, Istanbul, Turkey

    • AM

      Ahmad Mohammadi

      Professor
      Seyed Shohada Hospital, Esfahan Hemophilia Treatment Centre, Esfahan, Iran
      Esfahan, Esfahan, Iran

    • Mehran Karimi, MD

      Professor
      Shiraz University of Medical Sciences, Shiraz, Iran
      Shiraz, Fars, Iran

    • BY

      Bariş Yılmaz

      Professor
      Marmara University, Istanbul, Turkey
      Istanbul, Istanbul, Turkey

    • Canan Albayrak, MD (she/her/hers)

      Professor
      Ondokuz Mayis University, Faculty of Medicine, Samsun, Turkey
      Samsun, Samsun, Turkey

    • BT

      Burçak Tatli Güneş

      Professor
      Tepecik Education and Research Hospital, Izmir, Turkey
      Izmir, Izmir, Turkey

    • Zühre Kaya, MD

      Professor
      Gazi University Faculty of Medicine, Department of Pediatric Hematology
      Ankara, Ankara, Turkey

    • YA

      Yilmaz Ay

      Professor
      Pamukkale University Faculty of Medicine, Denizli, Turkey
      Denizli, Denizli, Turkey

    • SA

      Sinan Akbayram

      Professor
      Gaziantep University Faculty of Medicine, Gaziantep, Turkey
      Gaziantep, Gaziantep, Turkey

    • Hale Ören, MD (she/her/hers)

      Department of Pediatric Hematology
      Dokuz Eylül University Faculty of Medicine
      İzmir, Izmir, Turkey

    • Flora Peyvandi, MD, PhD (she/her/hers)

      Director
      IRCCS Ca' Granda Maggiore Hospital Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy; Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milano, Italy
      Milano, Lombardia, Italy

    Background: In 2016, the SIPPET study reported that in previously untreated patients (PUPs) with severe haemophilia A (HA) the choice of plasma-derived FVIII (pdFVIII) products in the first 50 exposure days (EDs) is associated with a significantly lower incidence of inhibitors compared to recombinant FVIII (rFVIII) products. However, the choice of FVIII product class after this high‐risk period has been subject of debate. It has been established that switching products in multi-transfused patients (>150 EDs) does not affect the risk of inhibitor development which becomes approximately 100 times lower in these previously treated patients (PTPs).

    Aims: To investigate whether a switch from pdFVIII to rFVIII in PUPs after the early high‐risk period would follow the expected low-risk pattern of inhibitor incidence as reported in PTPs, or a novel peak of inhibitors would appear due to the switch.

    Methods: We designed a survey on the ISTH REDCap platform to investigate the rate of novel inhibitors after switching PUPs between 50 and 150 EDs (Figure 1.A). Centres who did the switch on PUPs under 6 years old with severe HA according to this strategy, were invited to participate. By setting the rule-out risk at 7% and supposing 1 inhibitor incidence, a sample size of 80 was calculated to conclude with 80% power.

    Results: Twelve Turkish, 3 Iranian, 1 German and 1 Egyptian centre participated. Ninety-seven surveys were analysed among which 88 patients satisfied all eligibility criteria (Figure 1.B). Patients were switched at a median of 60 (50 – 73) EDs and received a median of 112 (100 – 260) EDs with rFVIII after the switch (Table 1.A). One patient developed an inhibitor post-switch (Table 1.B).

    Conclusion(s): Results from the PUP-SWITCH showed for the first time that a switch from pdFVIII to rFVIII after 50 EDs is safe and not associated with an additional risk of inhibitor incidence.

    Learning Objectives:

    • become familiar with the PUP-SWITCH: a multicenter, retrospective, observational study
    • gain insight into the low rate of inhibitor incidence upon a switch from plasma-derived to recombinant FVIII in PUPs with severe hemophilia A, after 50 EDs
    • acknowledge the results of the PUP-SWITCH study, in favor of the safety of the switch strategy to combine the beneficial features of both classes of FVIII products (plasma-derived and recombinant) each at their respective useful time