Immune tolerance induction in haemophilia A patients with inhibitor using Fc fusion recombinant factor VIII product

Abstract

Fc-fusion recombinant factor VIII product (rFVIIIFc), an extended half-life product, lowers an antigenicity against coagulation factor protein by increasing the regulatory T cell and indicates the tolerance is induced and promoted in animal models. Therefore, immune tolerance induction (ITI) is expecting its efficacy for haemophilia patients with inhibitor. It has been reported that some cases who underwent the ITI using rFVIIIFc showed a shorter duration than the use of conventional product until their inhibitors disappeared. We experienced three cases of haemophilia patients with inhibitor performed ITI using rFVIIIFc. Two of 3 cases developed on severe type of haemophilia A and the rest one did on mild type. ITI was performed in one patients as primary and two had as rescue ITI. The inhibitors in two patients disappeared in 77 weeks and 61 weeks, respectively, of which one disappeared in 9 weeks after changing to rFVIIIFc. The successful time courses were as same as previous ITI reports with conventional products. Whereas prophylactic use of bypass agents during ITI was performed in all cases, no severe bleedings and adverse reactions were observed. These results suggest that rFVIIIFc may be an effective option for both primary and rescue ITI.