Incidence and risk factors for inhibitor development in previously untreated severe haemophilia A patients born between 2005 and 2010

• Published in: Haemophilia : the official journal of the World Federation of Hemophilia 2014-11, Vol.20 (6), p.771-776
• Main Authors: Vézina, C., Carcao, M., Infante-Rivard, C., Lillicrap, D., Stain, A. M., Paradis, E., Teitel, J., Rivard, G. E.
• Format: Article
• Language: English
• Subjects: anti-FVIII; Blood Coagulation Factor Inhibitors - blood; Blood Coagulation Factor Inhibitors - immunology; Canada - epidemiology; Child, Preschool; danger signal; environment; Factor VIII - genetics; Factor VIII - therapeutic use; Follow-Up Studies; haemophilia A; Health Care Surveys; Hemophilia A - diagnosis; Hemophilia A - drug therapy; Hemophilia A - epidemiology; Hemophilia A - immunology; Humans; Incidence; Infant; Infant, Newborn; inhibitor; Isoantibodies - blood; Isoantibodies - immunology; Male; Mutation; Odds Ratio; PUP; Retrospective Studies; Risk Factors; Treatment Outcome
• ISSN: 1351-8216; 1365-2516
• DOI: 10.1111/hae.12479

Summary 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.