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

J Thromb Haemost. 2012 Mar;10(3):359-67. doi: 10.1111/j.1538-7836.2011.04611.x.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00243386.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Coagulants / administration & dosage*
  • Coagulants / adverse effects
  • Coagulants / pharmacokinetics
  • Drug Administration Schedule
  • Drug Monitoring
  • Europe
  • Factor VIII / administration & dosage*
  • Factor VIII / adverse effects
  • Factor VIII / pharmacokinetics
  • Hemophilia A / blood
  • Hemophilia A / complications
  • Hemophilia A / drug therapy*
  • Hemorrhage / blood
  • Hemorrhage / etiology
  • Hemorrhage / prevention & control*
  • Humans
  • Male
  • Middle Aged
  • Recombinant Proteins / administration & dosage
  • Time Factors
  • Treatment Outcome
  • United States
  • Young Adult

Substances

  • Coagulants
  • Recombinant Proteins
  • F8 protein, human
  • Factor VIII

Associated data

  • ClinicalTrials.gov/NCT00243386