title: Tailored prophylaxis in severe hemophilia A: interim results from the first 5 years of the Canadian Hemophilia Primary Prophylaxis Study.
abstract: BACKGROUND
  Prophylactic treatment for severe hemophilia A is likely to be more effective than treatment when bleeding occurs, however, prophylaxis is costly. We studied an inception cohort of 25 boys using a tailored prophylaxis approach to see if clotting factor use could be reduced with acceptable outcomes.
  
  
  METHODS
  Ten Canadian centers enrolled subjects in this 5-year study. Children were followed every 3 months at a comprehensive care hemophilia clinic. They were initially treated with once-weekly clotting factor; the frequency was escalated in a stepwise fashion if unacceptable bleeding occurred. Bleeding frequency, target joint development, physiotherapy and radiographic outcomes, as well as resource utilization, were determined prospectively.
  
  
  RESULTS
  The median follow-up time was 4.1 years (total 96.9 person-years). The median time to escalate to twice-weekly therapy was 3.42 years (lower 95% confidence limit 2.05 years). Nine subjects developed target joints at a rate of 0.09 per person-year. There was an average of 1.2 joint bleeds per person-year. The cohort consumed on average 3656 IU kg(-1)year(-1) of factor (F) VIII. Ten subjects required central venous catheters (three while on study); no complications of these devices were seen. One subject developed a transient FVIII inhibitor. End-of-study joint examination scores--both clinically and radiographically--were normal or near-normal.
  
  
  CONCLUSIONS
  Most boys with severe hemophilia A will probably have little bleeding and good joint function with tailored prophylaxis, while infusing less FVIII than usually required for traditional prophylaxis.
authors.affiliation: Division of Rheumatology, Hospital for Sick Children, Toronto, ON, Canada. brian.feldman@sickkids.ca
authors.forename: B M
authors.initials: BM
authors.lastname: Feldman
authors.forename: M
authors.initials: M
authors.lastname: Pai
authors.forename: G E
authors.initials: GE
authors.lastname: Rivard
authors.forename: S
authors.initials: S
authors.lastname: Israels
authors.forename: M-C
authors.initials: MC
authors.lastname: Poon
authors.forename: C
authors.initials: C
authors.lastname: Demers
authors.forename: S
authors.initials: S
authors.lastname: Robinson
authors.forename: K-H
authors.initials: KH
authors.lastname: Luke
authors.forename: J K M
authors.initials: JK
authors.lastname: Wu
authors.forename: K
authors.initials: K
authors.lastname: Gill
authors.forename: D
authors.initials: D
authors.lastname: Lillicrap
authors.forename: P
authors.initials: P
authors.lastname: Babyn
authors.forename: M
authors.initials: M
authors.lastname: McLimont
authors.forename: V S
authors.initials: VS
authors.lastname: Blanchette
mesh_terms: D002170:Canada; D002675:Child, Preschool; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005169:Factor VIII / Q000008:administration & dosage / Q000627:therapeutic use*; D006395:Hemarthrosis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007223:Infant; D007596:Joints / Q000473:pathology; D008297:Male; D010349:Patient Compliance; D017060:Patient Satisfaction; D011446:Prospective Studies
chemical_list: C078147:F8 protein, human; D005169:Factor VIII