The Author Journal Compilation ª

Abstract

Summary Factor IX (FIX) inhibitors develop in 1AE5-3% of haemophilia B patients. Due to its low incidence compared with that in haemophilia A, few comparable data exist on host and treatment-related risk factors, and immunological processes associated with FIX inhibitor development. Moreover, the safety and efficacy of bypass therapy as well as the outcome predictors of successful inhibitor eradication have been poorly characterised. The lack of a useful evidence-based approach to the diagnosis and management of FIX inhibitors complicates their significant morbidity due to the frequency of allergic reactions that often herald antibody development. This review discusses what is currently known about the epidemiology, natural history and immunology of anti-FIX antibody development. It addresses several special considerations in the approach to the treatment of bleeding and inhibitor eradication. A case is made for moving forward with an integrated international collaboration for the further study of the nature and treatment of this problem. Keywords: haemophilia B, factor IX deficiency, inhibitors, inhibitor treatment, immune tolerance. Factor IX (FIX) inhibitors develop in 1AE5-3% of haemophilia B patients, with geographically isolated pockets of higher incidence This review discusses what is currently known about the epidemiology, the natural history, the host and treatmentrelated risk factors, and the immunology of anti-FIX antibody development. It also addresses several special considerations in the clinical approach to both the safe and efficacious treatment of bleeding in the presence of antibody as well as inhibitor eradication, i.e. immune tolerance. A case is made for moving forward with an integrated international collaboration for the scientific and clinical study of the nature and treatment of this orphan disease in need of our attention. Epidemiology of FIX inhibitors: potential reasons for a low incidence disorder The published incidence of FIX inhibitors is between 1AE5 and 3% of all patients with haemophilia B and between 9 and 23% of severely affected FIX deficient patient