title: Once-weekly prophylactic treatment vs. on-demand treatment with nonacog alfa in patients with moderately severe to severe haemophilia B.
abstract: BACKGROUND
  Limited data are available on optimal prophylaxis regimens of factor IX (FIX) replacements for patients with haemophilia B.
  
  
  OBJECTIVE
  This multicentre, open-label study evaluated the efficacy and safety of once-weekly prophylaxis with nonacog alfa compared with on-demand treatment in adolescent and adult patients.
  
  
  METHODS
  Males aged 12-65 years with moderately severe to severe haemophilia B (FIX:C ≤ 2%) were eligible for enrolment. Patients received on-demand treatment for 26 weeks, followed by once-weekly prophylaxis of 100 IU kg(-1) for 52 weeks. The primary efficacy end point was the annualized bleeding rate (ABR). Secondary end points included response to on-demand treatment, the number of infusions used to treat bleeding events, and the incidence of less-than-expected therapeutic effect (LETE). FIX:C was measured on day 1 and at weeks 26 and 78.
  
  
  RESULTS
  Mean (±SD) ABR was lower during prophylaxis vs. on-demand treatment [3.6 (±4.6) vs. 32.9 (±17.4) events, respectively; P < 0.0001]. The majority (88.4%) of bleeding events had excellent or good responses upon the first infusion; 82.1% of events responded to the first infusion. No incident of LETE occurred. No thrombotic events or FIX inhibitors were reported. Eight of 17 FIX:C approximately 1 week after dosing were >2 IU dL(-1) (min-max of 2.13-10.39 IU dL(-1) ).
  
  
  CONCLUSIONS
  Once-weekly prophylaxis of 100 IU kg(-1) was associated with lower ABR compared with on-demand treatment in adolescents and adults with moderately severe to severe haemophilia B. Once-weekly prophylaxis was well tolerated, with a similar safety profile as that reported during the on-demand treatment period. Residual FIX:C may be supportive of effectiveness.
authors.affiliation: Department of Pediatric Hematology, Ege University Children's Hospital, Izmir, Turkey.
authors.forename: K
authors.initials: K
authors.lastname: Kavakli
authors.affiliation: Pfizer Inc, Collegeville, PA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Smith
authors.affiliation: University of Wroclaw, Wroclaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Kuliczkowski
authors.affiliation: Pfizer Inc, Collegeville, PA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Korth-Bradley
authors.affiliation: Eulji University, Daejeon, Korea.
authors.forename: C W
authors.initials: CW
authors.lastname: You
authors.affiliation: Pfizer Inc, Collegeville, PA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Fuiman
authors.affiliation: University Hospital Centre Rebro, Zagreb, Croatia.
authors.forename: S
authors.initials: S
authors.lastname: Zupančić-Šalek
authors.affiliation: National Blood Centre in Kuala Lumpur, Kuala Lumpur, Malaysia.
authors.forename: F
authors.initials: F
authors.lastname: Abdul Karim
authors.affiliation: Pfizer Inc, Collegeville, PA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Rendo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003029:Coagulants / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005164:Factor IX / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D002836:Hemophilia B / Q000188:drug therapy*; D006470:Hemorrhage / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D013927:Thrombosis / Q000209:etiology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003029:Coagulants; D011994:Recombinant Proteins; D005164:Factor IX
keywords: BeneFIX; factor IX; haemophilia B; pharmacokinetics; prevention; safety