Immune tolerance induction in haemophilia A patients with high-responding inhibitors to factor VIII: experience at a single institution

Inhibitor antibodies to transfused factor VIII pose significant challenges in the management of haemophilia A patients. The main concern is the inefficacy of replacement therapy in patients with high-titre antibodies, who have a shorter life-span and a greater morbidity compared to subjects without inhibitors. The ultimate goal in treating these patients is to eliminate the inhibitor antibody entirely, allowing the recommencement of specific replacement therapy. The results of an immune tolerance regimen based on pharmacokinetic parameters are reported here. In 12 high-responder haemophilia A patients immune tolerance induction (ITI) was attempted with daily administration of factor VIII concentrates of very high purity, either plasma-derived or produced by recombinant-DNA technology. Patients were given 100 IU kg(-1) day(-1) until the inhibitor was shown to be absent by at least two negative assays 1 month apart, with normal recovery of infused factor VIII and normal half-life (> 6 h), as assessed after a 3-day washout period. After the patient was judged to be inhibitor-free, immune tolerance treatment was continued with unmodified factor VIII doses for 2 months. Doses were thereafter gradually reduced and finally, regular prophylaxis by administration of 25 TU kg(-1) three times weekly was instituted. Immune tolerance was achieved in 10 of the 12 patients (including six of seven with long-standing inhibitors) within a median time of 8 months. Outcome of immune tolerance was not influenced by age at start of ITI nor by the interval between inhibitor development and ITI. The success rate and the inhibitor disappearance time of our immune tolerance regimen, utilizing high-purity factor VIII, agrees with those reported by other investigators.