Tailored prophylaxis in severe hemophilia A: interim results from the first 5 years of the Canadian Hemophilia Primary Prophylaxis Study.
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.
Feldman
B M
BM
Division of Rheumatology, Hospital for Sick Children, Toronto, ON, Canada. brian.feldman@sickkids.ca
Pai
M
M
Rivard
G E
GE
Israels
S
S
Poon
M-C
MC
Demers
C
C
Robinson
S
S
Luke
K-H
KH
Wu
J K M
JK
Gill
K
K
Lillicrap
D
D
Babyn
P
P
McLimont
M
M
Blanchette
V S
VS
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
C078147:F8 protein, human; D005169:Factor VIII