title: A review of immune tolerance induction with Haemate P in haemophilia A.
abstract: Immune tolerance induction (ITI) has been shown to successfully eliminate factor VIII (FVIII) inhibitors in haemophilia patients with inhibitors. We performed a literature search to identify reports from January 1980 to October 2012 on the use of the plasma-derived, von Willebrand factor (VWF)-containing FVIII concentrate Haemate P/Humate-P in the setting of ITI. Six reports were identified that specifically evaluated the use of Haemate P/Humate-P including 32 children and 9 adults. Dosing regimens ranged from 20 IU kg(-1) every 2-3 days in patients with low-responding (LR; n = 5) inhibitors to 300 IU kg(-1) day(-1) in patients with high-responding (HR; n = 36) inhibitors. Complete success was achieved in all five LR patients, in all three HR patients with good prognostic factors (age ≤7 years, pre-ITI inhibitor titre <10 BU, historical inhibitor titre <200 BU, time between inhibitor detection and ITI start <2 years), and in 24 of 33 (73%) HR patients with poor prognostic factors. The time to complete success was 0.5-4 months in good-prognosis patients and 0.5-42 months in poor-prognosis patients. Few adverse events were observed during ITI, and no cases of inhibitor relapse were reported with follow-up periods of up to 12 years. On the basis of this retrospective review of a diverse range of studies and case reports, we conclude that Haemate P/Humate-P for ITI in patients with inhibitors is effective and produces high rates of ITI success.
authors.affiliation: HZRM - Haemophilia Centre Rhein Main, Frankfurt-Moerfelden, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Escuriola Ettingshausen
authors.forename: W
authors.initials: W
authors.lastname: Kreuz
mesh_terms: D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D005169:Factor VIII / Q000627:therapeutic use*; D005260:Female; D006467:Hemophilia A / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D008297:Male; D014841:von Willebrand Factor / Q000627:therapeutic use*
chemical_list: D004338:Drug Combinations; C509423:factor VIII, von Willebrand factor drug combination; D014841:von Willebrand Factor; D005169:Factor VIII
keywords: Haemate P; factor VIII; haemophilia; immune tolerance induction; inhibitors; von Willebrand factor