title: ITI choice for the optimal management of inhibitor patients - from a clinical and pharmacoeconomic perspective.
abstract: The development of alloantibody inhibitors against factor VIII (FVIII) represents the most significant complication of haemophilia care. Inhibitors tend to develop early in the course of treatment in about 20-30% of patients with severe haemophilia who receive on-demand or prophylactic FVIII therapy. Many factors are associated with inhibitor formation, including disease severity, major FVIII gene defects, family history and non-Caucasian race, as well as age at first treatment, intensity of early treatment, use of prophylaxis and product choice. As these latter treatment-related variables are modifiable, they provide opportunity to minimize inhibitor incidence at the clinical level. Data from the Bonn Centre in Germany have indicated an overall success rate of 78% for immune tolerance induction (ITI) therapy, with a failure rate of 15% and with some treatments either ongoing (3%) or withdrawn (4%). Similarly, data from the G-ITI study, the largest international multicentre ITI study using a single plasma-derived (pd) FVIII/von Willebrand factor (VWF) product, have demonstrated success rates (complete and partial) in primary and rescue ITI of 87% and 74%, respectively, with 85% of poor prognosis patients achieving success. Favourable clinical results based on success rates and time to tolerization continue to be reported for use of pdFVIII/VWF in ITI, with pdFVIII/VWF having a particular role in patients who require rescue ITI and those with a poor prognosis for success. Data from prospective, randomized, controlled clinical studies, such as RES.I.ST (Rescue Immune Tolerance Study), are eagerly awaited. Another factor to consider with ITI therapy is cost; preliminary data from an updated decision analytic model have provided early evidence that ITI has an economic advantage compared with on-demand or prophylactic therapy.
authors: Institute for Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany.
authors: J
authors: J
authors: Oldenburg
authors: S K
authors: SK
authors: Austin
authors: C M
authors: CM
authors: Kessler
mesh_terms: D019774:Blood Coagulation Factor Inhibitors / Q000097:blood; D003029:Coagulants / Q000276:immunology / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D005169:Factor VIII / Q000037:antagonists & inhibitors / Q000276:immunology / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy* / Q000191:economics / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology; D014841:von Willebrand Factor / Q000037:antagonists & inhibitors / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D003029:Coagulants; D014841:von Willebrand Factor; D005169:Factor VIII
keywords: decision analytic model; factor VIII; haemophilia A; immune tolerance induction therapy; inhibitors; prognosis