title: Safety and efficacy of recombinant factor VIIa by pediatric age cohort: reassessment of compassionate use and trial data supporting US label.
abstract: The relative safety and efficacy of recombinant activated coagulation factor VII (rFVIIa, NovoSeven® RT) across pediatric age cohorts is poorly defined. The objective of this analysis was to assess the safety and efficacy of rFVIIa in pediatric patients with congenital hemophilia with inhibitors (CHwI) in the clinical studies supporting the U.S. labeling.
  
  
  
  Pediatric data were derived from seven studies (five acute and two perioperative treatments) and pooled. All data were stratified by age (<2, 2 to <6, 6 to <12, and 12-16 years) and study category (acute treatment of bleeding episodes or surgery).
  
  
  
  The pediatric dataset included 172 patients; 144 received rFVIIa for the treatment of bleeding episodes and 28 for the control of bleeding perioperatively. Recombinant FVIIa was effective for 95.4% (1,026/1,076) of the evaluable bleeding episodes and had similar treatment effectiveness across pediatric age groups (range, 94.1-97.2%). The majority received doses of 90 mcg/kg. rFVIIa was effective in achieving perioperative hemostasis across pediatric age groups (range, 91-100%), with greater efficacy observed with the recommended (90 mcg/kg) versus lower dose (35 mcg/kg). A total of 88 pediatric patients experienced a total of 285 adverse drug reactions, similar in type to those reported among adult patients. A total of seven thrombotic events were recorded in seven pediatric patients; only one was confirmed related to rFVIIa upon individual case review.
  
  
  
  rFVIIa is safe and effective in the treatment of bleeding episodes and prevention of periprocedure bleeding in CHwI with no apparent differences observed among pediatric age groups.
authors.affiliation: Dana-Farber/Boston Children's Cancer & Blood Disorders Center, Boston Hemophilia Center, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Stacy E
authors.initials: SE
authors.lastname: Croteau
authors.affiliation: Indiana Hemophilia and Thrombosis Center, Indianapolis, Indiana.
authors.forename: Charles
authors.initials: C
authors.lastname: Nakar
authors.affiliation: Dana-Farber/Boston Children's Cancer & Blood Disorders Center, Boston Hemophilia Center, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Ellis J
authors.initials: EJ
authors.lastname: Neufeld
authors.affiliation: Indiana Hemophilia and Thrombosis Center, Indianapolis, Indiana.
authors.forename: Amy
authors.initials: A
authors.lastname: Shapiro
authors.affiliation: Clinical, Medical and Regulatory Affairs, Novo Nordisk Inc, Plainsboro, New Jersey.
authors.forename: David L
authors.initials: DL
authors.lastname: Cooper
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D057176:Compassionate Use Trials; D015942:Factor VIIa / Q000009:adverse effects / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D008297:Male; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa
keywords: hemophilia; hemostasis; inhibitors; rFVIIa