Primary prophylaxis in children with severe haemophilia A and B-Implementation over the last 20 years as illustrated in real-world data in the PedNet cohorts.

Abstract

The prophylactic regimen in children with severe haemophilia is suggested in various publications and guidelines. Few data exist on its implementation in clinical practice. To investigate the implementation of primary prophylaxis based on real-life data from PedNet during the last 20 years. All children from the PedNet cohort (n=1260) with severe haemophilia A (SHA) or severe haemophilia B (SHB), FVIII/IX<.01 IU/mL, born between 2000 and 2009 (Cohort I; SHA n=662; SHB n=88) and 2010-2019 (Cohort II; SHA n=598; SHB n=94) were included. In SHA, the median age at start of prophylaxis was 17.3 months (IQR; 12.5-26.1) in Cohort I which decreased to 13.1 months (IQR; 10.4-19.1) in Cohort II (p<.000). "Once-a-week" prophylaxis at start increased from 49% to 68% (SHA) and 38% to 70% (SHB). FVIII doses were reduced from median 43.5 (IQR; 34.6-49.0) to 30.9IU/kg (IQR; 26.3-46.3), while dosing with FIX did not change. After 2010 approximately 60% of the patients with SHA and SHB started prophylaxis before any joint bleed. The number of CVADs needed in both cohorts was around 30%. Incidences of inhibitors were unchanged: SHA (∼31%) and SHB (∼10%). Sporadic cases were diagnosed significantly later (median 8.3 months; IQR; 3.7-11.9) and they had more joint bleeds before start of prophylaxis. Primary prophylaxis nowadays starts at an earlier age: before any joint bleed (60% of patients with SHA and SHB). Approximately 70% started on a once-weekly schedule with significantly reduced doses in SHA but unchanged in SHB.