A randomized comparison of two prophylaxis regimens and a paired comparison of on-demand and prophylaxis treatments in hemophilia A management

BACKGROUND Prophylaxis with factor (F)VIII is considered the optimal treatment for managing hemophilia A patients without inhibitors. OBJECTIVES To compare the efficacy of two prophylaxis regimens (primary outcome) and of on-demand and prophylaxis treatments (secondary outcome), and to continue the evaluation of immunogenicity and overall safety of the ADVATE Antihemophilic Factor (Recombinant), Plasma/Albumin Free Method (rAHF-PFM). PATIENTS/METHODS Previously on-demand-treated patients aged 7-59 years (n = 66) with FVIII levels ≤ 2% received 6 months of on-demand treatment and then were randomized to 12 months of either standard (20-40 IU kg(-1) every other day) or pharmacokinetic (PK)-tailored (20-80 IU kg(-1) every third day) prophylaxis, both regimens intended to maintain FVIII trough levels at or above 1%. Efficacy was evaluated in terms of annualized bleeding rates (ABRs). As subjects were first treated on-demand and then on prophylaxis, statistical comparisons between these treatments were paired. RESULTS Twenty-two (33.3%) subjects on prophylaxis experienced no bleeding episodes, whereas none treated on-demand were free from an episode of bleeding. ABRs for the two prophylaxis regimens were comparable, whereas differences between on-demand and either prophylaxis were statistically significant (P < 0.0001): median (interquartile range [IQR]) ABRs were 43.9 (21.9), 1.0 (3.5), 2.0 (6.9) and 1.1 (4.9) during on-demand treatment, standard, PK-tailored and any prophylaxis, respectively. There were no differences in FVIII consumption or adverse event rates between prophylaxis regimens. No subject developed FVIII inhibitors. CONCLUSIONS The present study demonstrates comparable safety and effectiveness for two prophylaxis regimens and that prophylaxis significantly reduces bleeding compared with on-demand treatment. PK-tailored prophylaxis offers an alternative to standard prophylaxis for the prevention of bleeding.