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Comparative effectiveness of full‐length and B‐domain deleted factor VIII for prophylaxis – a meta‐analysis
Author(s) -
Gruppo R. A.,
Brown D.,
Wilkes M. M.,
Navickis R. J.
Publication year - 2003
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1046/j.1365-2516.2003.00769.x
Subject(s) - medicine , incidence (geometry) , confidence interval , pooled analysis , gastroenterology , cumulative incidence , meta analysis , surgery , cohort , physics , optics
Summary. 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.