title: Factor VIII products and inhibitor development in severe hemophilia A.
abstract: BACKGROUND
  For previously untreated children with severe hemophilia A, it is unclear whether the type of factor VIII product administered and switching among products are associated with the development of clinically relevant inhibitory antibodies (inhibitor development).
  
  
  METHODS
  We evaluated 574 consecutive patients with severe hemophilia A (factor VIII activity, <0.01 IU per milliliter) who were born between 2000 and 2010 and collected data on all clotting-factor administration for up to 75 exposure days. The primary outcome was inhibitor development, which was defined as at least two positive inhibitor tests with decreased in vivo recovery of factor VIII levels.
  
  
  RESULTS
  Inhibitory antibodies developed in 177 of the 574 children (cumulative incidence, 32.4%); 116 patients had a high-titer inhibitory antibody, defined as a peak titer of at least 5 Bethesda units per milliliter (cumulative incidence, 22.4%). Plasma-derived products conferred a risk of inhibitor development that was similar to the risk with recombinant products (adjusted hazard ratio as compared with recombinant products, 0.96; 95% confidence interval [CI], 0.62 to 1.49). As compared with third-generation full-length recombinant products (derived from the full-length complementary DNA sequence of human factor VIII), second-generation full-length products were associated with an increased risk of inhibitor development (adjusted hazard ratio, 1.60; 95% CI, 1.08 to 2.37). The content of von Willebrand factor in the products and switching among products were not associated with the risk of inhibitor development.
  
  
  CONCLUSIONS
  Recombinant and plasma-derived factor VIII products conferred similar risks of inhibitor development, and the content of von Willebrand factor in the products and switching among products were not associated with the risk of inhibitor development. Second-generation full-length recombinant products were associated with an increased risk, as compared with third-generation products. (Funded by Bayer Healthcare and Baxter BioScience.).
authors: Department of Pediatrics, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors: Samantha C
authors: SC
authors: Gouw
authors: Johanna G
authors: JG
authors: van der Bom
authors: Rolf
authors: R
authors: Ljung
authors: Carmen
authors: C
authors: Escuriola
authors: Ana R
authors: AR
authors: Cid
authors: Ségolène
authors: S
authors: Claeyssens-Donadel
authors: Christel
authors: C
authors: van Geet
authors: Gili
authors: G
authors: Kenet
authors: Anne
authors: A
authors: Mäkipernaa
authors: Angelo Claudio
authors: AC
authors: Molinari
authors: Wolfgang
authors: W
authors: Muntean
authors: Rainer
authors: R
authors: Kobelt
authors: George
authors: G
authors: Rivard
authors: Elena
authors: E
authors: Santagostino
authors: Angela
authors: A
authors: Thomas
authors: H Marijke
authors: HM
authors: van den Berg
mesh_terms: D000906:Antibodies / Q000097:blood*; D002648:Child; D005169:Factor VIII / Q000276:immunology / Q000627:therapeutic use*; D006467:Hemophilia A / Q000276:immunology / Q000628:therapy*; D006801:Humans; D008297:Male; D014841:von Willebrand Factor / Q000032:analysis / Q000276:immunology
chemical_list: D000906:Antibodies; D014841:von Willebrand Factor; C427184:recombinant factor VIII SQ; D005169:Factor VIII