title: Immune tolerance therapy utilizing factor VIII/von Willebrand factor concentrate in haemophilia A patients with high titre factor VIII inhibitors.
abstract: Factor VIII (FVIII) inhibitors remain a serious complication of treatment for patients with haemophilia A. Immune tolerance induction (ITI) can eliminate inhibitors in the majority of patients, but there are major concerns related with this therapy. Investigators have raised the possibility that the use of FVIII/von Willebrand factor (FVIII/VWF) concentrates may improve the success rate of ITI and may shorten the duration of therapy necessary to attain tolerance. This retrospective study describes 25 patients at five institutions in the USA, who were treated with FVIII/VWF concentrate as part of their ITI. These were all patients who were considered poor prognosis because of clinical and laboratory characteristics, which made ITI less likely to be successful or because of a poor response to initial ITI with a monoclonal/recombinant FVIII concentrate. Overall success (complete tolerization) was 32% with another 40% attaining partial tolerization, but not complete tolerization. Of those patients attaining only partial tolerization, two patients ultimately discontinued ITI and had return of their high titre inhibitors. Eight percent of patients failed to attain either partial or complete tolerization and discontinued ITI. Another 24% are continuing with ITI but have titres of >10 BU. This study adds further retrospective data to the information regarding the use of FVIII/VWF concentrate in ITI.
authors.affiliation: Children's Hospitals and Clinics of Minnesota, Minneapolis, MN, USA.
authors.forename: M A H
authors.initials: MA
authors.lastname: Kurth
authors.forename: D
authors.initials: D
authors.lastname: Dimichele
authors.forename: C
authors.initials: C
authors.lastname: Sexauer
authors.forename: J M
authors.initials: JM
authors.lastname: Sanders
authors.forename: M
authors.initials: M
authors.lastname: Torres
authors.forename: S C
authors.initials: SC
authors.lastname: Zappa
authors.forename: M
authors.initials: M
authors.lastname: Ragni
authors.forename: N
authors.initials: N
authors.lastname: Leonard
mesh_terms: D000906:Antibodies / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005169:Factor VIII / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007223:Infant; D012189:Retrospective Studies; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000627:therapeutic use*
chemical_list: D000906:Antibodies; D014841:von Willebrand Factor; C078147:F8 protein, human; D005169:Factor VIII