Inhibitor development in non-severe haemophilia across Europe

Background: Evidence about inhibitor formation in non-severe haemophilia and the potential role for clotting factor concentrate type is scant.
Aim: To report inhibitor development in non-severe haemophilia patients enrolled in the European Haemophilia Safety Surveillance (EUHASS) study.
Methods: Inhibitors are reported quarterly and total treated patients annually. Incidence rates and 95% Confidence Intervals (95% CI) were calculated according to diagnosis and concentrate used.
Results: Between 1-10-2008 and 31-12-2012, 68 centres reported on 7969 patients with non-severe haemophilia A and 1863 patients with non-severe haemophilia B. For haemophilia A, 37 inhibitors occurred in 8622 treatment years, resulting in an inhibitor rate of 0.43/100 treatment years (95% CI 0.30-0.59). Inhibitors occurred at a median age of 35 years, after a median of 38 exposure days (EDs; P25-P75: 20-80); with 72% occurring within the first 50 EDs. In haemophilia B, one inhibitor was detected in 2149 treatment years, resulting in an inhibitor rate of 0.05/100 years (CI 0.001-0.26). This inhibitor developed at age 6 years, after 6 EDs. The rate of inhibitors appeared similar across recombinant and plasma derived FVIII concentrates. Rates for individual concentrates could not be calculated at this stage due to low number of events.
Conclusion: Inhibitors in non-severe haemophilia occur three times more frequently than in previously treated patients with severe haemophilia at a rate of 0.43/100 patient years (haemophilia A) and 0.05/100 years (haemophilia B). Although the majority of Inhibitors developed in the first 50 EDs, inhibitor development continued with increasing exposure to FVIII.
peer-reviewed