title: Prophylaxis vs. on-demand treatment with Nuwiq(®) (Human-cl rhFVIII) in adults with severe haemophilia A.
abstract: BACKGROUND
  Haemophilia A is treated with FVIII, either prophylactically or on demand. Prophylaxis is the gold standard in children and evidence is accumulating in adults.
  
  
  OBJECTIVE
  The aim of this analysis was to compare prophylaxis vs. on-demand treatment with Nuwiq(®) (Human-cl rhFVIII), a new-generation rFVIII expressed in a human cell line, in previously treated patients (PTPs) with severe haemophilia A. Data were analysed from two similarly designed, multinational, prospective, open-label studies with similar inclusion and exclusion criteria and comparable patient demographics. Human-cl rhFVIII was administered either prophylactically in a study of 32 adults or on-demand in a study of 22 patients (20 adults and two adolescents).
  
  
  RESULTS
  Patients treated prophylactically experienced 36 bleeds compared with 997 bleeds in patients treated on-demand (mean observation periods: 180 and 335 days respectively). Based on a negative binomial regression model, annualized bleeding rate (ABR) during prophylaxis was 2.30 (95% CI: 1.54, 3.44) compared with 57.74 (95% CI: 43.36, 76.91) during on-demand treatment, which equates to a 96% lower ABR during prophylaxis. 'Excellent' or 'good' efficacy in the treatment of bleeds was achieved with Human-cl rhFVIII in 100% of 28 evaluated bleeds during the prophylaxis study and 94.5% of 985 evaluated bleeds during the on-demand study. No inhibitors, treatment-related serious adverse events or severe adverse events were recorded during prophylaxis or or-demand treatment.
  
  
  CONCLUSIONS
  Prophylaxis with Human-cl rhFVIII reduces recurrent bleeding in adult PTPs with severe haemophilia A and adds further supportive evidence for the benefits of prophylaxis in adults.
authors.affiliation: Hannover Medical School, Clinic for Haematology, Haemostaseology, Oncology and Stem Cell Transplantation, Hannover, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Tiede
authors.affiliation: Institute of Experimental Haematology and Transfusion Medicine, Bonn, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Oldenburg
authors.affiliation: Specialised Hospital for Active Treatment "Joan Pavel", Sofia, Bulgaria.
authors.forename: T
authors.initials: T
authors.lastname: Lissitchkov
authors.affiliation: Octapharma AG, Lachen, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Knaub
authors.affiliation: Octapharma AG, Lachen, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Bichler
authors.affiliation: University of Colorado, Hemophilia and Thrombosis Center, Aurora, CO, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Manco-Johnson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003029:Coagulants / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005169:Factor VIII / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy* / Q000473:pathology; D006470:Hemorrhage / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003029:Coagulants; D011994:Recombinant Proteins; D005169:Factor VIII
keywords: Human-cl rhFVIII; Nuwiq; PTPs; haemophilia A; on-demand; prophylaxis