title: Integrated analysis of safety data from 12 clinical interventional studies of plasma- and albumin-free recombinant factor VIII (rAHF-PFM) in haemophilia A.
abstract: BACKGROUND
  Antihaemophilic factor (recombinant), plasma/albumin-free method (rAHF-PFM) is a human recombinant full-length factor VIII (FVIII) approved worldwide for the control and prevention of bleeding episodes, routine prophylaxis and perioperative management in adults and children with haemophilia A.
  
  
  OBJECTIVE
  To evaluate rAHF-PFM safety [including adverse events (AEs) and inhibitor incidence] from 12 interventional studies spanning >10 years.
  
  
  METHODS
  The study population comprised 418 treated patients (median age = 18.7 years) with FVIII levels ≤2% of normal, including 55 previously untreated or minimally treated patients (PUPs/MTPs) from all rAHF-PFM phase I-IV studies, excluding observational safety studies.
  
  
  RESULTS
  Most AEs were non-serious; only 93 AEs in 45 patients (10.8%) were related to rAHF-PFM. A total of 106 serious AEs (SAEs) occurred in 69 patients (16.5%); the most common were FVIII inhibitors (4.1%), device-related infection (1.0%) and pyrexia (0.7%). The 17 SAEs considered related to treatment consisted of FVIII inhibitors in 1 previously treated patient (PTP) (≤5 Bethesda Units [BU]) and 16 PUPs/MTPs [7/55 high titre (>5 BU), 12.7%; 9/55 low titre (≤5 BU), 16.4%]. Overall, the incidence of FVIII inhibitors was 0.36% in PTPs and 29.1% in PUPs/MTPs. No deaths or cases of hypersensitivity related to rAHF-PFM occurred.
  
  
  CONCLUSIONS
  This integrated safety analysis evaluated the safety and tolerability of rAHF-PFM in children and adults with moderately severe or severe haemophilia A in all interventional studies completed to date. It was important to review consolidated evidence as some AEs are rare. There were no new safety signals in a wide variety of clinical settings.
authors.affiliation: Indiana Hemophilia and Thrombosis Center, Indianapolis, IN, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Shapiro
authors.affiliation: Global Medical Affairs, Baxter Healthcare, Westlake Village, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Schoenig-Diesing
authors.affiliation: Biostatistics Department, Baxter Healthcare Corporation, Westlake Village, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Silvati-Fidell
authors.affiliation: Research and Development, Baxter Healthcare, Westlake Village, CA, USA.
authors.forename: W Y
authors.initials: WY
authors.lastname: Wong
authors.affiliation: Global Medical Affairs, Baxter Healthcare, Westlake Village, CA, USA.
authors.forename: V
authors.initials: V
authors.lastname: Romanov
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D005169:Factor VIII / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012449:Safety
chemical_list: D011994:Recombinant Proteins; D005169:Factor VIII
keywords: ADVATE; antihaemophilic factor (recombinant), plasma/albumin-free method; factor VIII; haemophilia A; inhibitors; integrated safety analysis