title: Incidence and risk factors for inhibitor development in previously untreated severe haemophilia A patients born between 2005 and 2010.
abstract: The objective of this study was to evaluate the inhibitor development (ID) in previously untreated patients (PUPs) with severe haemophilia A (FVIII ≤ 0.01 IU mL(-1) ). All Canadian Haemophilia Treatment Centres completed a questionnaire on patients born between September 2005 and August 2010 and followed for up to 7 years. Eligible patients had at least 20 exposure days (ED) or had developed an inhibitor. The odds ratio (OR) and 95% confidence intervals (95% CI) for risk factors to develop an inhibitor were estimated using unconditional logistic regression. A total of 99 haemophilia A PUPs were studied. Thirty-four (34%) developed an inhibitor (24/34 of high titre). Inhibitors developed in 25/63 (40%) patients with a high-risk mutation. ID was most frequent in Aboriginals (86%). Dose intensity (IU kg(-1)  day(-1) X number of ED) at first exposure to factor VIII (FVIII) was associated with a crude OR increase of 1.10 (95% CI: 0.99-1.23) with each increase of 100 dose-intensity units. Haemarthrosis and intracranial bleeding as the indication for first exposure to FVIII concentrate were associated with a crude OR for ID of 7.63 (95% CI: 2.14-27.17) and 5.08 (95% CI: 1.11-23.31) respectively. ID according to FVIII concentrate used was: Advate (®) 18/50 (36%), Kogenate FS(®) or Helixate FS(®) 15/36 (42%), Wilate(®) 0/11 and Xyntha(®) 1/2. In multivariate analysis, Aboriginal ethnicity (OR = 11.69; 95% CI: 1.11-122.86) and haemarthrosis (OR = 4.49; 95% CI: 1.08-18.61) were statistically significant. The cumulative incidence of ID in severe haemophilia A PUPs was 34% and varied according to ethnicity, type of bleeding at first ED, type of FVIII product and dose intensity at first exposure.
authors.affiliation: Division of Hematology/Oncology, CHU Sainte-Justine, Montréal, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Vézina
authors.forename: M
authors.initials: M
authors.lastname: Carcao
authors.forename: C
authors.initials: C
authors.lastname: Infante-Rivard
authors.forename: D
authors.initials: D
authors.lastname: Lillicrap
authors.forename: A M
authors.initials: AM
authors.lastname: Stain
authors.forename: E
authors.initials: E
authors.lastname: Paradis
authors.forename: J
authors.initials: J
authors.lastname: Teitel
authors.forename: G E
authors.initials: GE
authors.lastname: Rivard
mesh_terms: D019774:Blood Coagulation Factor Inhibitors / Q000097:blood / Q000276:immunology*; D002170:Canada / Q000453:epidemiology; D002675:Child, Preschool; D005169:Factor VIII / Q000235:genetics / Q000627:therapeutic use; D005500:Follow-Up Studies; D019538:Health Care Surveys; D006467:Hemophilia A / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology* / Q000276:immunology*; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007518:Isoantibodies / Q000097:blood / Q000276:immunology; D008297:Male; D009154:Mutation; D016017:Odds Ratio; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D007518:Isoantibodies; D005169:Factor VIII
keywords: PUP; anti-FVIII; danger signal; environment; haemophilia A; inhibitor