Inhibitor development is the most problematic and costly complication of haemophilia treatment. Inhibitor development depends on a complex multifactorial immune response that is influenced by patient- and treatment-related factors. Considerable research is focussed on inhibitor development as well as the mechanism of eradication through immune tolerance induction (ITI). Once an inhibitor develops, two general treatment options are available: to treat acute bleeds through bypassing agents, and to eradicate the inhibitor permanently through ITI. Previously untreated haemophilia A patients (PUPs) are at greatest risk of inhibitor development within the first 20 exposure days to factor VIII (FVIII). Inhibitor incidence in PUP studies ranges from 0% to as high as 52%. Plasma-derived FVIII concentrates have repeatedly been shown in cohort studies to be associated with a decreased inhibitor risk compared with recombinant FVIII concentrates, but results from randomized clinical trials are lacking; although one such trial is ongoing (SIPPET study). The occurrence of an inhibitor represents a major hardship for the patient and his family, and can result in high morbidity and a significant reduction in quality of life. Inhibitor eradication often requires the need for demanding and expensive treatment strategies aimed at inducing immune tolerance or bypassing the inhibitor. The role of von Willebrand factor (VWF) in immunoprotection is currently under review. The high-purity, pasteurized, plasma-derived FVIII concentrate, Beriate(®), contains sufficient amounts of VWF to not only bind all FVIII molecules but also provide additional FVIII binding sites, and may have additional beneficial effects that reduce the general immunogenicity of FVIII.
Keywords: Costs; Cumulative risk of inhibitor development; Haemophilia A; Inhibitors; Previously untreated patients; Risk management.
© 2013.