title: Current view and outcome of ITI therapy - A change over time?
abstract: BACKGROUND
  Inhibitor development in people with haemophilia is a serious complication that may require intensive and costly interventions. The goal of inhibitor management should be permanent inhibitor eradication through immune tolerance induction (ITI), but well-designed studies are lacking and the management of patients is therefore defined by the experience and views of the clinician.
  
  
  OBJECTIVE
  To explore the current clinical practice and outcome of ITI therapy in Europe and how this may have changed over the last decade, as well as to provide consensus recommendations to guide clinicians in their clinical practice.
  
  
  METHODS
  A survey was conducted among 16 European haemophilia comprehensive care centres to evaluate current ITI treatment regimens and success rates in severe and mild/moderate haemophilia A and haemophilia B. In addition, an updated literature review was performed as guidance for providing recommendations.
  
  
  RESULTS
  We demonstrated successful inhibitor treatment in 86% of severe haemophilia A patients with low responding (LR) and 59% of patients with high responding (HR) inhibitors. Some new trends in the management of patients with inhibitors were identified, including a tendency to use low-dose regimens (<50IU/kg/d) in both children and adults with HR inhibitors possibly based on similar success rates demonstrated in the I-ITI study compared to a high-dose protocol. Data on ITI therapy in mild and moderate haemophilia as well as haemophilia B were limited.
  
  
  CONCLUSIONS
  The outcome of ITI therapy seems to be stable over time, and treatment regimens remain heterogeneous. The use of low dose regimens however is considered more frequently.
authors: University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. Electronic address: k.holstein@uke.de.
authors: K
authors: K
authors: Holstein
authors: National Hemophilia Center, Dept. of Hematology and Transfusion Medicine, School of Medicine of Comenius University and University Hospital, Bratislava, Slovakia.
authors: A
authors: A
authors: Batorova
authors: Department of Transfusion Medicine and Blood Bank, Centre of Haemophilia, Centro Hospitalar São João, Porto, Portugal.
authors: M
authors: M
authors: Carvalho
authors: Department of Pediatric Hematology, Academic Medical Center, Amsterdam, Netherlands.
authors: K
authors: K
authors: Fijnvandraat
authors: Department of Haematology, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Norway.
authors: P
authors: P
authors: Holme
authors: Ege University Children's Hospital, Dept. Hematology, Izmir, Turkey.
authors: K
authors: K
authors: Kavakli
authors: Centre de traitement des hemophiles, Hopital de Bicetre AP-HP, Le Kremlin Bicetre, France.
authors: T
authors: T
authors: Lambert
authors: Hemophilia and Thrombosis Center, San Giovanni Bosco Hospital, Napoli, Italy.
authors: A
authors: A
authors: Rocino
authors: Unidad de Hemofilia, Hospital La Paz, Madrid, Spain.
authors: V
authors: V
authors: Jiménez-Yuste
authors: Department for Hematology and Vascular Disorders, Skåne University Hospital, Malmö/Lund, Sweden.
authors: J
authors: J
authors: Astermark
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D005060:Europe; D005260:Female; D006467:Hemophilia A / Q000276:immunology / Q000628:therapy*; D002836:Hemophilia B / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007108:Immune Tolerance; D007165:Immunosuppression Therapy / Q000009:adverse effects / Q000379:methods*; D008297:Male; D016896:Treatment Outcome; D055815:Young Adult
keywords: Haemophilia; ITI regimens; Immune tolerance induction; Immunosuppression; Inhibitors