title: Comparative effectiveness of full-length and B-domain deleted factor VIII for prophylaxis--a meta-analysis.
abstract: Recently reported data suggest the possibility of differences in clinical efficacy between full-length factor VIII (FL-FVIII) and B-domain deleted recombinant factor VIII (BDD-rFVIII). To address this question, we conducted a meta-analysis of studies reporting the incidence of bleeding under prophylaxis, as well as studies of FL-FVIII and BDD-rFVIII half-life. The pooled cumulative weekly prophylactic dose of BDD-rFVIII (81.3 +/- 13.8 IU kg(-1) week(-1)) was greater by 36% (P = 0.11) than that of FL-FVIII (60.0 +/- 5.9 IU kg(-1) week(-1)). The pooled incidence of bleeding in BDD-rFVIII recipients [16.8 bleeds per patient year; confidence interval (CI), 9.5-24.2 bleeds per patient year] was more than 2.5-fold larger (P < 0.0005) than that in patients receiving FL-FVIII (6.6 bleeds per patient year; CI, 4.7-8.5 bleeds per patient year). In a multivariate analysis, the incidence rate ratio was 2.10 (CI, 1.98-2.24), indicating that breakthrough bleeding under prophylaxis was more than twice as likely with BDD-rFVIII than FL-FVIII at equivalent doses and ages. The pooled half-life for plasma-derived FL-FVIII (13.7 h; CI, 12.8-14.6 h) was closely similar to that for recombinant FL-FVIII (14.3 h; CI, 13.3-15.4 h). By contrast, the pooled half-life for BDD-rFVIII (11.3 h; CI, 9.9-12.7 h) was shorter by approximately 3 h compared with FL-FVIII. Although the results of the meta-analysis need to be interpreted with caution, the pooled data suggest that breakthrough bleeding under prophylaxis may occur more frequently in patients receiving BDD-rFVIII than FL-FVIII and may at least partly reflect a more abbreviated half-life of BDD-rFVIII. Several biochemical differences between BDD-rFVIII and FL-FVIII may underlie the observed disparities in bleeding incidence and half-life. This meta-analysis should be confirmed by further studies.
authors.affiliation: The Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA. ralph.gruppo@cchmc.org
authors.forename: R A
authors.initials: RA
authors.lastname: Gruppo
authors.forename: D
authors.initials: D
authors.lastname: Brown
authors.forename: M M
authors.initials: MM
authors.lastname: Wilkes
authors.forename: R J
authors.initials: RJ
authors.lastname: Navickis
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005169:Factor VIII / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006207:Half-Life; D006395:Hemarthrosis / Q000209:etiology / Q000517:prevention & control*; D006467:Hemophilia A / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D008297:Male; D015999:Multivariate Analysis; D010446:Peptide Fragments / Q000097:blood / Q000627:therapeutic use
chemical_list: C451034:B-domain-deleted factor VIII; D010446:Peptide Fragments; D005169:Factor VIII