Real-world data shows emicizumab works early in hemophilia A infants
A new registry study of 80 infants starting emicizumab prophylaxis found the drug safely controlled bleeding in most cases, with roughly half requiring additional factor VIII treatment. The findings extend clinical trial evidence into everyday practice, helping manufacturers and healthcare systems understand how the subcutaneous therapy performs outside controlled settings.
Originaltitel: FVIII exposure, bleeding outcomes, and inhibitor development in 80 PUPs and MTPs with severe hemophilia A on emicizumab prophylaxis: real world data from the PedNet Registry.
Emicizumab som subcutan profylax hos små barn med svår hemofili A säkrar blödningskontroll men utsätter för fördröjd FVIII-exponering och oförändrad inhibitorriskökning. I en prospektiv registerstudie från PedNet följdes 80 spädbarn (39 förut obehandlade, 41 minimalt behandlade) under median 19,5 månader. Endast 59 procent fick FVIII under perioden — med första exponering först vid 21,2 månader för de tidigare obehandlade. Den genomsnittliga årlig blödningsfrekvensen uppgick till 0,6, och ingen allvarlig biverkan registrerades. Dock utvecklade fem spädbarn (två tidigare obehandlade) FVIII-inhibitorer, motsvarande 35,2 procent kumulativ incidans. Forskare från Skåne University Hospital och andra institutioner i Sverige, Israel, Storbritannien och Tjeckien deltar i registret. För inköpsansvariga och regulatorer är resultatet kritiskt: profylax med emicizumab kan inte automatiskt reducera inhibitorrisken under barndomen, vilket påverkar långtidsbehandlingsväljandet.
BACKGROUND: Subcutaneous emicizumab prophylaxis is increasingly used for early prophylaxis in infants with severe hemophilia A (SHA). Although the HAVEN 7 trial reported on 55 infants with SHA, real-world information regarding FVIII exposure, inhibitor development and bleeding on this age group remains limited. OBJECTIVES: To describe FVIII exposure, model-based annualized bleeding rate (ABR), and FVIII inhibitor development in infants with SHA starting emicizumab prophylaxis as previously untreated patients (PUPs) or minimally treated patients (MTPs; 1-5 FVIII-exposure days (EDs)). PATIENTS/METHODS: Data on PUPs and MTPs with SHA on emicizumab for ≥12 weeks were extracted from the prospective, observational multicenter PedNet Registry on 01-01-2025, Participants in HAVEN 7 were excluded. FVIII exposure and inhibitor development were determined by survival analysis. Written informed consent was obtained from all parents/guardians. RESULTS: This study included 80 infants (39 PUPs) starting emicizumab at median 8.6 months followed for median 19.5 months. During follow-up, 47/80 (59%) infants received FVIII for bleeding and/or concomitant 'prophylaxis' (n=10), with delayed first exposure at median 5.0 (MTPs) and 21.2 months (PUPs), respectively. Mean ABR was 0.6/year (95%CI 0.4-1.1). Five infants (2 PUPs) developed FVIII inhibitors after 4-18 EDs, cumulative incidence of 35.2% (95%CI 8.6-61.7). No serious adverse events or thrombosis were reported. CONCLUSION: These data show delayed FVIII exposure and good bleeding control without adverse events. Preliminary analysis suggested no decrease in FVIII inhibitor development. PedNet will continue to collect data needed to reliably assess the influence of different FVIII exposure during emicizumab prophylaxis on FVIII inhibitor development in PUPs.