Trends in Treatment of Severe Haemophilia and Impact on Inhibitor Assessment by the EUHASS Registry

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.