title: Use of Haemate(®)  P as immune tolerance induction in patients with severe haemophilia A who failed previous induction attempts: a multicentre observational study.
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.
authors.affiliation: Centre de Référence de l'Hémophilie, Hôpital Necker-Enfants Malades AP-HP, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Rothschild
authors.forename: R
authors.initials: R
authors.lastname: D'Oiron
authors.forename: A
authors.initials: A
authors.lastname: Borel-Derlon
authors.forename: Y
authors.initials: Y
authors.lastname: Gruel
authors.forename: R
authors.initials: R
authors.lastname: Navarro
authors.forename: C
authors.initials: C
authors.lastname: Negrier
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003029:Coagulants / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D004338:Drug Combinations; D005169:Factor VIII / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D005602:France; D006467:Hemophilia A / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D055815:Young Adult; D014841:von Willebrand Factor / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D003029:Coagulants; D004338:Drug Combinations; C509423:factor VIII, von Willebrand factor drug combination; D014841:von Willebrand Factor; D005169:Factor VIII