Randomized, prospective clinical trial of recombinant factor VIIa for secondary prophylaxis in hemophilia patients with inhibitors.
BACKGROUND
Hemophilic patients with factor VIII (FVIII) and FIX inhibitors suffer from frequent bleeding episodes and reduced quality of life.


OBJECTIVE
To evaluate whether secondary prophylaxis with activated recombinant factor VII (rFVIIa) can safely and effectively reduce bleeding frequency as compared to conventional on-demand therapy.


METHODS
Thirty-eight male patients entered a 3-month preprophylaxis period to confirm high baseline bleeding frequency (mean > or = 4 bleeds per month). Twenty-two patients were randomized 1:1 to receive daily rFVIIa prophylaxis with either 90 or 270 microg kg(-1) for 3 months, followed by a 3-month postprophylaxis period.


RESULTS
Bleeding frequency was reduced by 45% and 59% during prophylaxis with 90 and 270 microg kg(-1), respectively (P < 0.0001); however, there was no significant difference detected between doses. The majority of this reduction was maintained during the postprophylaxis period. Although all types of bleed were similarly reduced, the effect was most pronounced for spontaneous joint bleeds. Patients reported significantly fewer hospital admissions and days absent from work/school during prophylaxis as compared to the preprophylaxis period. No thromboembolic events were reported during prophylaxis.


CONCLUSIONS
Clinically relevant reductions in bleeding frequency during prophylaxis as compared to conventional on-demand therapy were achieved without raising safety concerns. These results provide evidence for the concept of secondary rFVIIa prophylaxis in inhibitor patients with frequent bleeds.
Konkle
B A
BA
Penn Comprehensive Hemophilia Program, University of Pennsylvania, PA 19104, USA. barbara.konkle@uphs.upenn.edu
Ebbesen
L S
LS
Erhardtsen
E
E
Bianco
R P
RP
Lissitchkov
T
T
Rusen
L
L
Serban
M A
MA
D000328:Adult; D002648:Child; D015942:Factor VIIa / Q000009:adverse effects / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy* / Q000503:physiopathology; D002836:Hemophilia B / Q000188:drug therapy* / Q000503:physiopathology; D006470:Hemorrhage / Q000517:prevention & control*; D006801:Humans; D008297:Male; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use
D011994:Recombinant Proteins; D015942:Factor VIIa