title: Inhibitor development in non-severe haemophilia across Europe.
abstract: Evidence about inhibitor formation in non-severe haemophilia and the potential role for clotting factor concentrate type is scant. It was the aim of this study to report inhibitor development in non-severe haemophilia patients enrolled in the European Haemophilia Safety Surveillance (EUHASS) study. Inhibitors are reported quarterly and total treated patients annually. Incidence rates and 95% confidence intervals (95% CI) were calculated according to diagnosis and concentrate used. Between 1-10-2008 and 31-12-2012, 68 centres reported on 7,969 patients with non-severe haemophilia A and 1,863 patients with non-severe haemophilia B. For haemophilia A, 37 inhibitors occurred in 8,622 treatment years, resulting in an inhibitor rate of 0.43/100 treatment years (95% CI 0.30-0.59). Inhibitors occurred at a median age of 35 years, after a median of 38 exposure days (EDs; P25-P75: 20-80); with 72% occurring within the first 50 EDs. In haemophilia B, one inhibitor was detected in 2,149 treatment years, resulting in an inhibitor rate of 0.05/100 years (95% CI 0.001-0.26). This inhibitor developed at the age of six years, after six EDs. The rate of inhibitors appeared similar across recombinant and plasma derived factor VIII (FVIII) concentrates. Rates for individual concentrates could not be calculated at this stage due to low number of events. In conclusion, inhibitors in non-severe haemophilia occur three times more frequently than in previously treated patients with severe haemophilia at a rate of 0.43/100 patient years (haemophilia A) and 0.05/100 years (haemophilia B). Although the majority of inhibitors developed in the first 50 EDs, inhibitor development continued with increasing exposure to FVIII.
authors: 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: Kathelijn
authors: K
authors: Fischer
authors: Alfonso
authors: A
authors: Iorio
authors: Riitta
authors: R
authors: Lassila
authors: Flora
authors: F
authors: Peyvandi
authors: Gabriele
authors: G
authors: Calizzani
authors: Alex
authors: A
authors: Gatt
authors: Thierry
authors: T
authors: Lambert
authors: Jerzy
authors: J
authors: Windyga
authors: Estelle A
authors: EA
authors: Gilman
authors: R
authors: R
authors: Hollingsworth
authors: Michael
authors: M
authors: Makris
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002648:Child; D003029:Coagulants / Q000009:adverse effects / Q000276:immunology*; D005060:Europe; D005169:Factor VIII / Q000009:adverse effects / Q000276:immunology*; D006467:Hemophilia A / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D002836:Hemophilia B / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000276:immunology; D012042:Registries; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D003029:Coagulants; D011994:Recombinant Proteins; C078147:F8 protein, human; D005169:Factor VIII
keywords: Factor VIII inhibitors; epidemiological studies; factor concentrates; haemophilia A / B; haemophilia therapy; non-severe haemophilia