title: Inhibitor development in haemophilia according to concentrate. Four-year results from the European HAemophilia Safety Surveillance (EUHASS) project.
abstract: Inhibitor development represents the most serious side effect of haemophilia treatment. Any difference in risk of inhibitor formation depending on the product used might be of clinical relevance. It was this study's objective to assess inhibitor development according to clotting factor concentrate in severe haemophilia A and B. The European Haemophilia Safety Surveillance (EUHASS) was set up as a study monitoring adverse events overall and according to concentrate. Since October 2008, inhibitors were reported at least quarterly. Number of treated patients was reported annually, specifying the number of patients completing 50 exposure days (Previously Untreated Patients, PUPs) without inhibitor development. Cumulative incidence, incidence rates and 95 % confidence intervals (CI) were calculated. Data from October 1, 2008 to December 31, 2012 were analysed for 68 centres that validated their data. Inhibitors developed in 108/417 (26 %; CI 22-30 %) PUPs with severe haemophilia A and 5/72 (7 %; CI 2-16%) PUPs with severe haemophilia B. For Previously Treated Patients (PTPs), 26 inhibitors developed in 17,667 treatment years [0.15/100 treatment years; CI 0.10-0.22) for severe haemophilia A and 1/2836 (0.04/100; (CI 0.00-0.20) for severe haemophilia B. Differences between plasma-derived and recombinant concentrates, or among the different recombinant FVIII concentrates were investigated. In conclusion, while confirming the expected rates of inhibitors in PUPs and PTPs, no class or brand related differences were observed.
authors.affiliation: Kathelijn Fischer, MD, PhD, Julius Center for Health Sciences and, Primary Care and Van Creveldkliniek, University Medical Center Utrecht, Room C01.425, PO Box 85500, 3508 GA Utrecht, The Netherlands, Tel.: +31 88 755 8450, Fax: +31 88 755 5438, E-mail: k.fischer@umcutrecht.nl.
authors.forename: Kathelijn
authors.initials: K
authors.lastname: Fischer
authors.forename: Riita
authors.initials: R
authors.lastname: Lassila
authors.forename: Flora
authors.initials: F
authors.lastname: Peyvandi
authors.forename: Gabriele
authors.initials: G
authors.lastname: Calizzani
authors.forename: Alex
authors.initials: A
authors.lastname: Gatt
authors.forename: Thierry
authors.initials: T
authors.lastname: Lambert
authors.forename: Jerzy
authors.initials: J
authors.lastname: Windyga
authors.forename: Alfonso
authors.initials: A
authors.lastname: Iorio
authors.forename: Estelle
authors.initials: E
authors.lastname: Gilman
authors.forename: Michael
authors.initials: M
authors.lastname: Makris
mesh_terms: D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D019774:Blood Coagulation Factor Inhibitors / Q000737:chemistry*; D002648:Child; D005060:Europe; D005169:Factor VIII / Q000009:adverse effects / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy*; D002836:Hemophilia B / Q000188:drug therapy; D006801:Humans; D015994:Incidence; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D011994:Recombinant Proteins; D005169:Factor VIII
keywords: Adverse Drug Reaction Reporting Systems; antibodies; factor VIII; haemophilia A; haemophilia B; neutralising