A Cochrane review included 6 studies with a total of 142 subjects.
Two studies compared three-times-a-week prophylactic administration with on-demand treatment in children with hemophilia. Pooled results from these two studies showed a rate ratio of 0.30 (95% Cl 0.12 to 0.76) for all bleedings and 0.22 (95% Cl 0.08 to 0.63) for joint bleedings favouring prophylaxis. Three of the remaining four studies evaluated hemophilia A; one showed a statistically significant decrease in frequency of joint bleeds with prophylaxis compared to placebo, with a rate difference of -10.73 (95% Cl-16.55 to -4.91) bleeds per year. Two studies compared two prophylaxis regimens, failing to demonstrate an advantage of one regimen over the other in terms of bleeding frequency. The fourth study evaluated hemophilia B and showed fewer joint bleeds with weekly (15 IU/kg) versus bi-weekly (7.5 IU/kg) prophylaxis, rate difference -3.30 (95% Cl -5.50 to -1.10) bleeds per year.
Three studies evaluated hemophilia A; one showed a decrease in frequency of joint bleeds with prophylaxis compared to placebo (non-physiological dose), with a rate difference (RD) –10.80 (95% confidence interval [CI] –16.33 to –5.27) bleeds per year. The remaining two studies evaluating hemophilia A compared two prophylaxis regimens, one study showed no difference in joint bleed frequency, RD –5.04 (95%CI –17.02 to 6.94) bleeds per year and another failed to demonstrate an advantage of factor VIII dosing based on individual pharmacokinetic data over the standard prophylaxis regimen with RD –0.14 (95% CI –1.34 to 1.05) bleeds per year. The fourth study evaluated hemophilia B and showed fewer joint bleeds with weekly (15 IU/kg) versus bi-weekly (7.5 IU/kg) prophylaxis, RD –3.30 (95% CI –5.50 to –1.10) bleeds per year. Current established pattern of practice to use clotting factor concentrates for primary prohylaxis is justified by 26 unique observational studies reporting 1612 people with hemophilia undergoing clotting factor concentrate prophylaxis in comparison with 1191 people with hemophilia treated on-demand. The observational studies of comparison to historical controls indicated clear benefits in the reduction of bleed frequency and joint deformity, and it has been very difficult for investigators to carry out RCTs since then.