title: Efficacy and safety of long-acting recombinant fusion protein linking factor IX with albumin in haemophilia B patients undergoing surgery.
abstract: BACKGROUND
  Recombinant factor IX fusion protein (rIX-FP) has been developed to improve the pharmacokinetic (PK) profile of factor IX (FIX), allowing maintenance of desired FIX activity between injections at extended intervals, ultimately optimizing haemophilia B treatment.
  
  
  OBJECTIVE
  To determine the efficacy and safety of rIX-FP in the perioperative setting.
  
  
  METHODS
  Subjects were adult and paediatric patients with severe to moderately severe haemophilia B (FIX ≤ 2%) participating in three Phase III clinical trials and undergoing a surgical procedure. PK profiles were established prior to surgery for each patient. Haemostatic efficacy was assessed by the investigator for up to 72 h after surgery. Safety measurements during the study included adverse events and inhibitors to FIX. FIX activity was monitored during and after surgery to determine if repeat dosing was required.
  
  
  RESULTS
  Twenty-one, both major and minor, surgeries were performed in 19 patients. Haemostatic efficacy was rated as excellent (n = 17) or good (n = 4) in all surgeries. A single preoperative dose maintained intraoperative haemostasis in 20 of 21 surgeries. Nine major orthopaedic surgeries were conducted in eight patients with a mean of 7 (range: 6-12) rIX-FP injections during surgery and the 14-day postoperative period. Median rIX-FP consumption for orthopaedic surgeries was 87 IU kg(-1) preoperatively and 375 IU kg(-1) overall. No subject developed inhibitors to FIX or antibodies to rIX-FP.
  
  
  CONCLUSIONS
  Recombinant factor IX fusion protein was well tolerated and effectively maintained haemostasis during and after surgery. Stable FIX activity was achieved with a prolonged dosing interval and reduced consumption compared to conventional or currently available long-acting recombinant FIX.
authors.affiliation: Centre Régional de Traitement de l'Hémophilie (CRTH)/Unite d'Hemostase Clinique, Hôpital Cardiologique Louis Pradel, University Lyon I, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Négrier
authors.affiliation: National Blood Centre, Kuala Lumpur, Malaysia.
authors.forename: F
authors.initials: F
authors.lastname: Abdul Karim
authors.affiliation: Perpetual Succour Hospital, Cebu City, Philippines.
authors.forename: L M
authors.initials: LM
authors.lastname: Lepatan
authors.affiliation: Centre Régional de Traitement de l'Hémophilie (CRTH)/Unite d'Hemostase Clinique, Hôpital Cardiologique Louis Pradel, University Lyon I, Lyon, France.
authors.forename: A
authors.initials: A
authors.lastname: Lienhart
authors.affiliation: Complexo Hospitalario Universitario A Coruňa, A Coruňa, Spain.
authors.forename: M F
authors.initials: MF
authors.lastname: López-Fernández
authors.affiliation: Haemophilia Clinic, Comprehensive Care Centre Charlotte Maxeke Johannesburg Academic Hospital and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.|NHLS South Africa, Johannesburg, South Africa.
authors.forename: J
authors.initials: J
authors.lastname: Mahlangu
authors.affiliation: Clinical Division of Haematology and Haemostaseology, Medical Clinic I, Medical University Vienna, Vienna, Austria.
authors.forename: I
authors.initials: I
authors.lastname: Pabinger
authors.affiliation: Clinical Research and Development, CSL Behring, King of Prussia, PA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Clinical Research and Development, CSL Behring, King of Prussia, PA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Wolko
authors.affiliation: Clinical Research and Development, CSL Behring, King of Prussia, PA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Voigt
authors.affiliation: Clinical Research and Development, CSL Behring, King of Prussia, PA, USA.
authors.forename: I
authors.initials: I
authors.lastname: Jacobs
authors.affiliation: A. Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Ca' Granda Foundation, Maggiore Hospital Policlinico, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Santagostino
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003029:Coagulants / Q000627:therapeutic use*; D005164:Factor IX / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D006207:Half-Life; D002836:Hemophilia B / Q000188:drug therapy* / Q000473:pathology; D006470:Hemorrhage / Q000517:prevention & control; D006801:Humans; D008875:Middle Aged; D011184:Postoperative Period; D011300:Preoperative Care; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000493:pharmacokinetics / Q000627:therapeutic use; D012709:Serum Albumin / Q000235:genetics* / Q000378:metabolism; D012720:Severity of Illness Index; D013514:Surgical Procedures, Operative; D055815:Young Adult
chemical_list: D003029:Coagulants; D011993:Recombinant Fusion Proteins; D012709:Serum Albumin; D005164:Factor IX
keywords: albumin fusion proteins; factor IX; haemophilia B; orthopaedic surgery; recombinant fusion proteins