Trends in Treatment of Severe Haemophilia and Impact on Inhibitor Assessment by the EUHASS Registry
Kathelijn Fischer 1); Riitta Lassila 2); Flora Peyvandi 3),4); Alex Gatt 5); Samantha C. Gouw 6), 7); Rob Hollingsworth 8); Thierry Lambert 1),9); Radoslaw Kaczmarek 10),11); Diana Carbonero 12); Michael Makris 13); the EUHASS participants
1 Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, University Utrecht, Utrecht, theNetherlands 2 Department of Hematology, Unit of Coagulation Disorders, Helsinki University Central Hospital, Research Program Unit in Systems Oncology,University of Helsinki, Helsinki, Finland 3 Angelo Bianchi Bonomi, Hemophilia and Thrombosis centre, Fondazione IRCCS Ca’ Granda Ospedale MaggiorePoliclinico, University of Milan, Milan, Italy 4 Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy 5 Mater Dei Hospital,Tal-QRoqq, Msida, Malta 6 Department of Pediatric Hematology, Emma Children’s Hospital, Amsterdam UMC location University of Amsterdam, Amsterdam,the Netherlands 7 Amsterdam Reproduction & Development, Public Health, Amsterdam UMC location University of Amsterdam, Amsterdam, theNetherlands 8 MDSAS, Manchester, UK 9 Reference Center for hemophilia and rare bleeding disorders, Hôpital Bicêtre, APHP, Université Paris Saclay, LeKremlin Bicêtre, Paris, France 10 Coagulation Products Safety Supply and Access Committee, World Federation of Hemophilia, Montreal, Quebec, Canada11 Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, USA 12 European Association of Haemophilia and AssociatedDisorders, Brussels, Belgium 13 School of Medicine and Population Health, University of Sheffield, Sheffield, UK
ABSTRACT
Background
The last 15 years have seen new extended half-life (EHL) recombinant FVIII/IX concentrates and nonreplacement therapy for haemophilia A (emicizumab) introduced in Europe. These changes affect FVIII/IX exposure in previously untreated patients (PUPs) and previously treated patients (PTPs) with severe haemophilia A and B (SHA and SHB) and may modify inhibitor development and/or detection.
Aim
To report trends in treatment for severe haemophilia and concomitant changes in inhibitor incidence.
Methods
Between 2008 and 2022, 97 centres reported inhibitor development against FVIII/IX concentrates to the European Haemophilia Safety Surveillance System (EUHASS). Inhibitors were reported quarterly, and PUPs without inhibitor development annually. Cumulative inhibitor incidences (95% confidence intervals [CI]) were calculated for PUPs and incidence rates/1000 years (CI) for PTPs.
Results
By 2022, SHA-PUPs (n = 1574) received emicizumab (44%), SHL-rFVIII (21.5%), pdFVIII (17.5%) and EHL-rFVIII (17%). SHB-PUPs (n = 236) received EHL-rFIX (79%) and SHL-rFIX (21%). SHA-PTPs (68,772 years) received EHL-rFVIII (31%), SHL-rFVIII (28%), emicizumab (25%), and pdFVIII (15%). SHB PTPs (11,185 years) received EHL-rFIX (69%), pdFIX (15%) and SHL-rFIX (15%). Observed Inhibitor incidence in SHA-PUPs decreased from 24% before 2016 to 6% in 2022 (p < 0.001), and potentially in SHB-PUPs too (from 9% to 3%; p = 0.066), but remained stable in SHA/SHB PTPs.
Conclusion
In 2022, 44% of SHA-PUPs and 25% of SHA-PTPs received emicizumab prophylaxis. Concomitantly, observed inhibitor incidence reduced to 6% in SHA-PUPs. In SHB, EHL-rFIX treatment increased to 79% in SHB-PUPs and 69% in SHB-PTPs. Assessing inhibitor incidence for new concentrates is likely to be hampered by novel treatments causing delayed exposure to FVIII/FIX.