Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia.
BACKGROUND
Effective ways to prevent arthropathy in severe hemophilia are unknown.


METHODS
We randomly assigned young boys with severe hemophilia A to regular infusions of recombinant factor VIII (prophylaxis) or to an enhanced episodic infusion schedule of at least three doses totaling a minimum of 80 IU of factor VIII per kilogram of body weight at the time of a joint hemorrhage. The primary outcome was the incidence of bone or cartilage damage as detected in index joints (ankles, knees, and elbows) by radiography or magnetic resonance imaging (MRI).


RESULTS
Sixty-five boys younger than 30 months of age were randomly assigned to prophylaxis (32 boys) or enhanced episodic therapy (33 boys). When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group were considered to have normal index-joint structure on MRI (P=0.006). The relative risk of MRI-detected joint damage with episodic therapy as compared with prophylaxis was 6.1 (95% confidence interval, 1.5 to 24.4). The mean annual numbers of joint and total hemorrhages were higher at study exit in the episodic-therapy group than in the prophylaxis group (P<0.001 for both comparisons). High titers of inhibitors of factor VIII developed in two boys who received prophylaxis; three boys in the episodic-therapy group had a life-threatening hemorrhage. Hospitalizations and infections associated with central-catheter placement did not differ significantly between the two groups.


CONCLUSIONS
Prophylaxis with recombinant factor VIII can prevent joint damage and decrease the frequency of joint and other hemorrhages in young boys with severe hemophilia A. (ClinicalTrials.gov number, NCT00207597 [ClinicalTrials.gov].).
Manco-Johnson
Marilyn J
MJ
University of Colorado and Health Sciences Center, Denver, USA. marilyn.manco-johnson@uchsc.edu
Abshire
Thomas C
TC
Shapiro
Amy D
AD
Riske
Brenda
B
Hacker
Michele R
MR
Kilcoyne
Ray
R
Ingram
J David
JD
Manco-Johnson
Michael L
ML
Funk
Sharon
S
Jacobson
Linda
L
Valentino
Leonard A
LA
Hoots
W Keith
WK
Buchanan
George R
GR
DiMichele
Donna
D
Recht
Michael
M
Brown
Deborah
D
Leissinger
Cindy
C
Bleak
Shirley
S
Cohen
Alan
A
Mathew
Prasad
P
Matsunaga
Alison
A
Medeiros
Desiree
D
Nugent
Diane
D
Thomas
Gregory A
GA
Thompson
Alexis A
AA
McRedmond
Kevin
K
Soucie
J Michael
JM
Austin
Harlan
H
Evatt
Bruce L
BL
D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005169:Factor VIII / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006395:Hemarthrosis / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy*; D006470:Hemorrhage / Q000517:prevention & control*; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D007592:Joint Diseases / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D016896:Treatment Outcome
C078147:F8 protein, human; D005169:Factor VIII