title: Long-term outcome of haemophilia A patients after successful immune tolerance induction therapy using a single plasma-derived FVIII/VWF product: the long-term ITI study.
abstract: BACKGROUND
  Immune tolerance induction (ITI) is a standard intervention to eradicate inhibitors in haemophilic patients. However, information on the long-term condition of patients who eradicated the inhibitor totally or partially after ITI is scarce.
  
  
  OBJECTIVE
  To perform a long-term follow-up to describe the status of patients reported as ITI success in the G-ITI study.
  
  
  METHODS
  This was an international, multicentre, observational, retrospective study of the 57 haemophilic patients who were reported as ITI success in the G-ITI study. Demographics and post-ITI clinical data recorded until January 2015 were extracted from the medical records. A descriptive analysis was undertaken.
  
  
  RESULTS
  Forty-four patients were evaluable. Post-ITI follow-up was 9.1 years in average. Thirty-seven target joints were affected in 21 patients; 38 patients presented bleeding with a mean of 1.0 ± 1.2 episodes year-1, most of them (271/330) treated with Fanhdi®(Grifols). Around half of the patients underwent at least one surgical procedure. Most venous access complications were of expected nature, requiring hospital stay in practically all cases. Fanhdi was used in 42 patients as the regular haemophilia treatment after ITI, mainly prophylactically. Three patients (6.8%) who were being treated with Fanhdi (prophylaxis), Kogenate (prophylaxis) and Emoclot (on demand), respectively, showed inhibitor relapse (at 29, 53 and 13 months after ITI, with 0.9, 3.65 and 12.5 BU respectively). All of them were successfully tolerized after rescue ITI.
  
  
  CONCLUSIONS
  After ITI success, all patients continued with regular successful FVIII treatment for haemophilia for more than 9 years. The few inhibitor relapses were successfully overcome after rescue ITI.
authors.affiliation: Haematology Department, Hospital Universitario La Paz, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Jiménez-Yuste
authors.affiliation: University Clinic Bonn, Institute of Experimental Haematology and Transfusion Medicine, Bonn, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Oldenburg
authors.affiliation: Haemophilia, Haemostasis & Thrombosis Centre, Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK.
authors.forename: S
authors.initials: S
authors.lastname: Rangarajan
authors.affiliation: Scientific and Medical Affairs Department, Grifols, Sant Cugat del Vallès, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Peiró-Jordán
authors.affiliation: Centro Emofilia e Trombosi "Angelo Bianchi Bonomi", Fondazione IRCCS Ca' Granda, Milano, ltalia.
authors.forename: E
authors.initials: E
authors.lastname: Santagostino
mesh_terms: D000328:Adult; D005169:Factor VIII / Q000627:therapeutic use*; D005260:Female; D006467:Hemophilia A / Q000188:drug therapy*; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics*; D008297:Male; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult; D014841:von Willebrand Factor / Q000627:therapeutic use*
chemical_list: D014841:von Willebrand Factor; C078147:F8 protein, human; D005169:Factor VIII
keywords: FVIII inhibitor; coagulation factor VIII; factor concentrate; haemophilia; immune tolerance; long-term