Immune tolerance induction with recombinant factor VIII in hemophilia A patients with high responding inhibitors

Haematologica. 2006 Apr;91(4):558-61.

Abstract

Immune tolerance induction (ITI) eradicates inhibitors in patients with hemophilia A. This study was designed to investigate the success rate of ITI in high-responding inhibitor patients with severe hemophilia A using recombinant factor VIII (rFVIII). Twenty-six patients received different ITI regimens until a normal recovery (>66%) and half-life (>6 h) of infused FVIII was achieved. In order to maximize the chance of success, the initiation of ITI was deferred in the majority of patients until the inhibitor declined to <10 BU. Twenty-two patients (85%) had baseline inhibitor levels <10 BU (median 2.3 BU) when ITI began. Within a median of 6 months, immune tolerance was achieved in 19 of 26 patients (73%) including 12/17 (70%) with intron 22 inversion, 5/7 (71%) with other null mutations and two with small deletion/insertions in the F8 gene. In conclusion, recombinant FVIII induces a high rate of immune tolerance even in carriers of null F8 mutations.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Factor VIII / therapeutic use*
  • Hemophilia A / drug therapy*
  • Hemophilia A / genetics
  • Hemophilia A / immunology
  • Humans
  • Immune Tolerance / drug effects*
  • Immune Tolerance / genetics
  • Infant
  • Isoantibodies / blood
  • Middle Aged
  • Mutation

Substances

  • Isoantibodies
  • F8 protein, human
  • Factor VIII