title: Indirect comparisons of efficacy and weekly factor consumption during continuous prophylaxis with recombinant factor VIII Fc fusion protein and conventional recombinant factor VIII products.
abstract: BACKGROUND
  Recombinant factor VIII (rFVIII) products with extended half-lives have the potential to improve adherence and outcomes in haemophilia beyond the results obtained with conventional rFVIII products.
  
  
  OBJECTIVE
  In the absence of head-to-head comparisons, annualized bleed rates (ABRs) and weekly factor consumption with rFVIII Fc fusion protein (rFVIIIFc) and conventional rFVIII products were indirectly compared using studies of continuous prophylaxis.
  
  
  METHODS
  A systematic literature review was conducted to identify studies of rFVIII products for comparison with rFVIIIFc in the continuous prophylactic treatment of previously treated adolescents and adults with moderate and severe haemophilia A. Mean ABRs were compared between rFVIIIFc and individual rFVIII studies and between rFVIIIFc and a pooled measure for rFVIII estimated by meta-analysis. Comparisons of factor consumption were based on mean or median weekly factor consumption.
  
  
  RESULTS
  Results from seven studies of conventional rFVIII products (injections 2-4 times week-1) were compared with rFVIIIFc (injections 1.4-2.4 times week-1). The pooled mean ABR for rFVIII products was significantly higher compared with rFVIIIFc (difference = 2.0; P = 0.007). Compared with most rFVIII studies, the reported weekly factor consumption was lower with rFVIIIFc [mean differences = 15.5-21.8 IU kg-1week-1(17-26%); median differences = 12.7-29.8 IU kg-1week-1(16-37%)]. In one comparison, mean weekly factor consumption with rFVIII was significantly lower but mean ABR was significantly higher than rFVIIIFc.
  
  
  CONCLUSIONS
  Prophylaxis with rFVIIIFc may be associated with improved bleeding rates and lower weekly factor consumption than more frequently injected rFVIII products. Relative to rFVIII products with similar bleeding rates, results indicate that rFVIIIFc is associated with reduced weekly factor consumption while requiring fewer prescribed injections.
authors.affiliation: McMaster University, Hamilton, ON, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Iorio
authors.affiliation: Biogen Hemophilia, Cambridge, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Krishnan
authors.affiliation: Sobi, Stockholm, Sweden.
authors.forename: K J
authors.initials: KJ
authors.lastname: Myrén
authors.affiliation: Sobi, Stockholm, Sweden.|University of Copenhagen, Copenhagen, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Lethagen
authors.affiliation: Analysis Group, Boston, MA, USA.
authors.forename: N
authors.initials: N
authors.lastname: McCormick
authors.affiliation: Analysis Group, Boston, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Yermakov
authors.affiliation: Analysis Group, Boston, MA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Karner
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D005169:Factor VIII / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control*; D006470:Hemorrhage / Q000150:complications; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics*; D008297:Male; D011993:Recombinant Fusion Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; D005169:Factor VIII
keywords: adherence; annualized bleed rate; factor VIII; haemophilia A; prophylaxis; recombinant