title: New findings on inhibitor development: from registries to clinical studies.
abstract: The high incidence of inhibitors against factor VIII (FVIII) concentrates in patients with haemophilia A has encouraged debate as to whether product-type plays a role. There is debate in the literature as to whether rFVIII concentrates are associated with a higher incidence of inhibitors compared to pdFVIII products. The management of haemophilia in patients with inhibitors includes on-demand/prophylaxis treatment with bypassing agents, and/or immune tolerance induction (ITI). However, these options create an economic and emotional burden on patients, their families and healthcare practitioners. Although ITI eliminates inhibitors successfully in 60-80% of cases, it is costly. Despite high costs, preliminary data from a decision analytical model have indicated that ITI is economically advantageous compared with on-demand/prophylactic treatment with bypassing agents. In patients with persistent inhibitors and those who are not candidates for ITI or have failed ITI, bleeding-related mortality and morbidity increase and quality of life decreases, compared with non-inhibitor patients. This article provides an update on the risk of inhibitor development and discusses best management approaches for patients with high-risk factors for inhibitor development.
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Peyvandi
authors.affiliation: HZRM - Haemophilia Centre Rhein Main, Frankfurt-Mörfelden, Germany.
authors.forename: C E
authors.initials: CE
authors.lastname: Ettingshausen
authors.affiliation: School of Medicine, University of Lille, Lille, France.
authors.forename: J
authors.initials: J
authors.lastname: Goudemand
authors.affiliation: Department of Haematology, Autónoma University Madrid and La Paz University Hospital, Madrid, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Jiménez-Yuste
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Santagostino
authors.affiliation: Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, Sheffield, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Makris
mesh_terms: D019774:Blood Coagulation Factor Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005169:Factor VIII / Q000037:antagonists & inhibitors*; D006467:Hemophilia A / Q000188:drug therapy*; D006801:Humans; D064887:Observational Studies as Topic; D016032:Randomized Controlled Trials as Topic
chemical_list: D019774:Blood Coagulation Factor Inhibitors; C078147:F8 protein, human; D005169:Factor VIII
keywords: factor VIII; factor concentrate; haemophilia A; inhibitor burden; inhibitor development; previously untreated patients