title: Switching clotting factor concentrates: considerations in estimating the risk of immunogenicity.
abstract: The development of neutralizing antibodies to factor VIII (FVIII) is the most serious complication of therapy for haemophilia A. There is now excellent documentation that a large number of both genetic and environmental factors contribute to the risk of FVIII inhibitor incidence. One of the environmental factors that has been proposed as an influence on this complication is the occurrence of FVIII product switching. There are only a small number of clinical studies that have addressed this question, and thus, the amount of objective information available to assess this association is limited. In this review, in addition to summarizing past evidence pertinent to this subject, we present the results of a complementary strategy, a Delphi analysis, to add to the considerations of product switching and FVIII immunogenicity. With the imminent arrival in the clinic of several new FVIII products, the haemophilia community must be prepared to collect prospectively controlled data to better address this important management issue.
authors.affiliation: Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Matino
authors.forename: D
authors.initials: D
authors.lastname: Lillicrap
authors.forename: J
authors.initials: J
authors.lastname: Astermark
authors.forename: G
authors.initials: G
authors.lastname: Dolan
authors.forename: C
authors.initials: C
authors.lastname: Kessler
authors.forename: T
authors.initials: T
authors.lastname: Lambert
authors.forename: M
authors.initials: M
authors.lastname: Makris
authors.forename: J
authors.initials: J
authors.lastname: O'Donnell
authors.forename: S
authors.initials: S
authors.lastname: Pipe
authors.forename: E
authors.initials: E
authors.lastname: Santagostino
authors.forename: J-M
authors.initials: JM
authors.lastname: Saint-Remy
authors.forename: W
authors.initials: W
authors.lastname: Schramm
authors.forename: A
authors.initials: A
authors.lastname: Iorio
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D057915:Drug Substitution; D005169:Factor VIII / Q000276:immunology* / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology*; D006801:Humans; D015994:Incidence
chemical_list: D057134:Antibodies, Neutralizing; D005169:Factor VIII
keywords: clotting factor concentrates; haemophilia; immunogenicity; inhibitors