title: Recombinant versus plasma-derived factor VIII products and the development of inhibitors in previously untreated patients with severe hemophilia A: the CANAL cohort study.
abstract: It has been suggested that plasma-derived factor VIII products induce fewer inhibitors than recombinant factor VIII products. We investigated the relationship of factor VIII product type and switching between factor VIII products with the risk to develop inhibitors. This multicenter retrospective cohort study included 316 patients with severe hemophilia A born between 1990 and 2000. The outcome was clinically relevant inhibitor development, defined as the occurrence of at least 2 positive inhibitor titers with decreased recovery. The risk of inhibitor development was not clearly lower in plasma-derived compared with recombinant factor VIII products (relative risk [RR], 0.8; 95% confidence interval [CI], 0.5-1.3). Among high-titer inhibitors, the possible reduction in risk was even less pronounced (RR, 0.9; CI, 0.5-1.5). Plasma-derived products with considerable quantities of von Willebrand factor (VWF) carried the same risk for inhibitor development as recombinant factor VIII products (RR, 1.0; CI, 0.6-1.6). Switching between factor VIII products did not increase the risk for inhibitors (RR, 1.1; CI, 0.6-1.8). In conclusion, our findings support neither the notion that plasma-derived factor VIII products with considerable concentrations of VWF confer a lower risk to develop inhibitory antibodies than recombinant factor VIII products, nor that switching between factor VIII product brands increases inhibitor risks in previously untreated patients with severe hemophilia A.
authors.affiliation: Van Creveldlkiniek, University Medical Center Utrrecht, Utrecht, The Netherlands.
authors.forename: Samantha C
authors.initials: SC
authors.lastname: Gouw
authors.forename: Johanna G
authors.initials: JG
authors.lastname: van der Bom
authors.forename: Günter
authors.initials: G
authors.lastname: Auerswald
authors.forename: Carmen Escuriola
authors.initials: CE
authors.lastname: Ettinghausen
authors.forename: Ulf
authors.initials: U
authors.lastname: Tedgård
authors.forename: H Marijke
authors.initials: HM
authors.lastname: van den Berg
mesh_terms: D000906:Antibodies / Q000097:blood / Q000276:immunology; D001779:Blood Coagulation Factors / Q000037:antagonists & inhibitors / Q000737:chemistry*; D002648:Child; D015331:Cohort Studies; D005169:Factor VIII / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy*; D006801:Humans; D008297:Male; D009154:Mutation; D010949:Plasma / Q000378:metabolism*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D012044:Regression Analysis; D012189:Retrospective Studies; D012306:Risk; D013997:Time Factors
chemical_list: D000906:Antibodies; D001779:Blood Coagulation Factors; D011994:Recombinant Proteins; C078147:F8 protein, human; D005169:Factor VIII