title: Factor VIII brand and the incidence of factor VIII inhibitors in previously untreated UK children with severe hemophilia A, 2000-2011.
abstract: The effect of recombinant factor VIII (rFVIII) brand on inhibitor development was investigated in all 407 severe hemophilia A previously untreated patients born in the United Kingdom (UK) between 1 January 2000 and 31 December 2011. Eighty-eight (22%) had been in the RODIN study. Information was extracted from the National Haemophilia Database. Because exposure days (EDs) were not known for some patients, time from first treatment was used as a surrogate for rFVIII exposure. An inhibitor developed in 118 (29%) patients, 60 high and 58 low titer, after a median (interquartile range) of 7.8 (3.3-13.5) months from first exposure and 16 (9-30) EDs. Of 128 patients treated with Kogenate Bayer/Helixate NexGen, 45 (35.2%, 95% confidence interval [CI] 27.4-43.8) developed an inhibitor compared with 42/172 (24.4%, 95% CI 18.6% to 31.4%) with Advate (P = .04). The adjusted hazard ratio (HR) (95% CI) for Kogenate Bayer/Helixate NexGen compared with Advate was 2.14 (1.12-4.10) (P = .02) for high titer and 1.75 (1.11-2.76) (P = .02) for all inhibitors. When excluding UK-RODIN patients, the adjusted HR (95% CI) for high-titer inhibitors was 2.00 (0.93-4.34) (P = .08). ReFacto AF was associated with a higher incidence of all, but not high-titer, inhibitors than Advate. These results will help inform debate around the relative immunogenicity and use of rFVIII brands.
authors.affiliation: Department of Haematology, University Hospital of Wales, School of Medicine, Cardiff, United Kingdom;
authors.forename: Peter W
authors.initials: PW
authors.lastname: Collins
authors.affiliation: The UK National Haemophilia Database, Manchester, United Kingdom;
authors.forename: Benedict P
authors.initials: BP
authors.lastname: Palmer
authors.affiliation: Department of Haematology, Royal Hospital for Sick Children, Glasgow, United Kingdom;
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Chalmers
authors.affiliation: The Haemophilia Centre, The Royal London Hospital, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom;
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Hart
authors.affiliation: The Haemophilia Centre, Great Ormond Street Hospital for Children National Health Service Foundation Trust, London, United Kingdom;
authors.forename: Ri
authors.initials: R
authors.lastname: Liesner
authors.affiliation: The Centre for Haemostasis and Thrombosis, Guys and St. Thomas's Hospital, London and the Haemophilia, Haemostasis and Thrombosis Centre, Hampshire Hospitals National Health Service Foundation Trust, Basingstoke, United Kingdom;
authors.forename: Savita
authors.initials: S
authors.lastname: Rangarajan
authors.affiliation: Department of Haematology, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom;
authors.forename: Katherine
authors.initials: K
authors.lastname: Talks
authors.affiliation: Department of Haematology, Birmingham Children's Hospital National Health Service Foundation Trust, Birmingham, United Kingdom; and.
authors.forename: Michael
authors.initials: M
authors.lastname: Williams
authors.affiliation: Department of Haematology, Manchester University, Manchester Royal Infirmary, Manchester, United Kingdom.
authors.forename: Charles R M
authors.initials: CR
authors.lastname: Hay
mesh_terms: D000917:Antibody Formation; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005169:Factor VIII / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy* / Q000453:epidemiology* / Q000276:immunology; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007518:Isoantibodies / Q000097:blood*; D012720:Severity of Illness Index; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D007518:Isoantibodies; C427184:recombinant factor VIII SQ; D005169:Factor VIII