title: Recombinant long-acting glycoPEGylated factor IX (nonacog beta pegol) in haemophilia B: assessment of target joints in multinational phase 3 clinical trials.
abstract: BACKGROUND
  The paradigm(™) 2 and 4 phase 3 clinical trials investigated the safety and efficacy of nonacog beta pegol, a recombinant glycoPEGylated factor IX (FIX) with extended half-life, in previously treated haemophilia B patients.
  
  
  OBJECTIVE
  These post hoc analyses investigated the bleeding patterns in target joints.
  
  
  METHODS
  Patients randomized to 40 or 10 IU kg(-1) once weekly prophylaxis who had at least one target joint were included. Baseline demographics and disease-specific data were collected. Bleeding patterns were assessed, and an International Society on Thrombosis and Haemostasis (ISTH) definition of target joints was used.
  
  
  RESULTS
  A total of 67% and 8% of patients in the 40 and 10 IU kg(-1) arm, respectively, did not experience target joint bleeds during the paradigm(™) 2 trial. Twenty-four target joints were recorded in each prophylaxis arm at baseline. During the paradigm(™) 2 trial, no bleeds were reported in 17 (71%) and 7 (29%) target joints in the 40 and 10 IU kg(-1) arms respectively. All target joint bleeds in the 40 IU kg(-1) once weekly prophylaxis arm were controlled with a single injection of 40 IU kg(-1) nonacog beta pegol. By the latest ISTH definition, 90% and 58% of target joints in the 40 and 10 IU kg(-1) arms, respectively, were no longer considered target joints at the end of the paradigm(™) 2 trial. At the end of the paradigm(™) 4 extension trial, all target joints in the 40 IU kg(-1) arm were no longer considered target joints.
  
  
  CONCLUSIONS
  Routine prophylaxis with 40 IU kg(-1) once weekly nonacog beta pegol has the potential for effective management of target joint bleeds in haemophilia B patients.
authors.affiliation: Hôpital Louis Pradel, University Claude Bernard Lyon 1, Bron, France.
authors.forename: C
authors.initials: C
authors.lastname: Negrier
authors.affiliation: Hemostasis and Thrombosis Center, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Young
authors.affiliation: Haemophilia Centre, National Blood Centre, Kuala Lumpur, Malaysia.
authors.forename: F
authors.initials: F
authors.lastname: Abdul Karim
authors.affiliation: Arthur Bloom Haemophilia Centre, Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: P W
authors.initials: PW
authors.lastname: Collins
authors.affiliation: Department of Haematology, Ogikubo Hospital, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hanabusa
authors.affiliation: Haemophilia Medical & Science, Novo Nordisk A/S, Soeborg, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Colberg
authors.affiliation: Haemophilia Biostatistics, Novo Nordisk A/S, Soeborg, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Goldman
authors.affiliation: Division of Hematology and Medical Oncology, Mount Sinai Medical Center, New York, NY, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Walsh
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003029:Coagulants / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005164:Factor IX / Q000627:therapeutic use*; D006207:Half-Life; D002836:Hemophilia B / Q000188:drug therapy*; D006470:Hemorrhage / Q000517:prevention & control; D006801:Humans; D007592:Joint Diseases / Q000453:epidemiology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003029:Coagulants; D011994:Recombinant Proteins; C000592276:nonacog beta pegol; D011092:Polyethylene Glycols; D005164:Factor IX
keywords: FIX; glycoPEGylated factor IX; haemophilia B; nonacog beta pegol; prophylaxis; target joint