Use of Haemate(®) P as immune tolerance induction in patients with severe haemophilia A who failed previous induction attempts: a multicentre observational study

Haemophilia. 2013 Mar;19(2):281-6. doi: 10.1111/hae.12018. Epub 2012 Oct 8.

Abstract

Immune tolerance induction (ITI) can eliminate factor VIII (FVIII) inhibitory antibodies that appear during FVIII replacement therapy. If first-line ITI fails, switching to a different FVIII concentrate, especially one containing von Willebrand factor (VWF), has been advocated. The objective of the study was to assess the efficacy and safety of Haemate(®) P, a plasma-derived FVIII concentrate containing high levels of VWF, as ITI in severe haemophilia A patients who had failed at least one prior ITI attempt with a different FVIII concentrate. In this multicentre, observational study, Haemate(®) P was administered at a starting dose of 83-308 IU kg(-1) day(-1) (1500-6000 IU day(-1)). Efficacy was assessed by standard criteria (e.g. Bethesda titre, FVIII recovery and half-life), and bleeding characteristics. Nine patients from six haemophilia centres were treated with Haemate(®) P after failing one (n = 2), two (n = 5) or three (n = 2) prior ITI courses. The median time from inhibitor detection to Haemate(®) P treatment was 5.4 years. The median Haemate(®) P dose was 134 IU kg(-1), and the median treatment duration 32 months. During median of 47 months of follow-up, complete response, partial response and treatment failure were observed in one, three and five patients respectively. Five patients experienced seven adverse events (AEs), including two serious AEs (sepsis). Haemate(®) P was discontinued due to an AE in one patient with a partial response. Haemate(®) P salvage ITI resulted in complete or partial tolerization in four of nine patients (44%) who had failed previous ITI attempts using different FVIII concentrates.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Coagulants / adverse effects
  • Coagulants / immunology
  • Coagulants / therapeutic use*
  • Drug Combinations
  • Factor VIII / adverse effects
  • Factor VIII / immunology
  • Factor VIII / therapeutic use*
  • France
  • Hemophilia A / drug therapy*
  • Hemophilia A / immunology
  • Humans
  • Immune Tolerance / drug effects*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Young Adult
  • von Willebrand Factor / adverse effects
  • von Willebrand Factor / immunology
  • von Willebrand Factor / therapeutic use*

Substances

  • Coagulants
  • Drug Combinations
  • factor VIII, von Willebrand factor drug combination
  • von Willebrand Factor
  • Factor VIII