A Iorio1, S Krishnan2, K J Myrén3, S Lethagen3,4, N McCormick5, S Yermakov5, P Karner5. 1. McMaster University, Hamilton, ON, Canada. 2. Biogen Hemophilia, Cambridge, MA, USA. 3. Sobi, Stockholm, Sweden. 4. University of Copenhagen, Copenhagen, Denmark. 5. Analysis Group, Boston, MA, USA.
Abstract
INTRODUCTION: Recombinant factor VIII (rFVIII) products with extended half-lives have the potential to improve adherence and outcomes in haemophilia beyond the results obtained with conventional rFVIII products. AIM: In the absence of head-to-head comparisons, annualized bleed rates (ABRs) and weekly factor consumption with rFVIII Fc fusion protein (rFVIIIFc) and conventional rFVIII products were indirectly compared using studies of continuous prophylaxis. METHODS: A systematic literature review was conducted to identify studies of rFVIII products for comparison with rFVIIIFc in the continuous prophylactic treatment of previously treated adolescents and adults with moderate and severe haemophilia A. Mean ABRs were compared between rFVIIIFc and individual rFVIII studies and between rFVIIIFc and a pooled measure for rFVIII estimated by meta-analysis. Comparisons of factor consumption were based on mean or median weekly factor consumption. RESULTS: Results from seven studies of conventional rFVIII products (injections 2-4 times week-1 ) were compared with rFVIIIFc (injections 1.4-2.4 times week-1 ). The pooled mean ABR for rFVIII products was significantly higher compared with rFVIIIFc (difference = 2.0; P = 0.007). Compared with most rFVIII studies, the reported weekly factor consumption was lower with rFVIIIFc [mean differences = 15.5-21.8 IU kg-1 week-1 (17-26%); median differences = 12.7-29.8 IU kg-1 week-1 (16-37%)]. In one comparison, mean weekly factor consumption with rFVIII was significantly lower but mean ABR was significantly higher than rFVIIIFc. CONCLUSION: Prophylaxis with rFVIIIFc may be associated with improved bleeding rates and lower weekly factor consumption than more frequently injected rFVIII products. Relative to rFVIII products with similar bleeding rates, results indicate that rFVIIIFc is associated with reduced weekly factor consumption while requiring fewer prescribed injections.
INTRODUCTION: Recombinant factor VIII (rFVIII) products with extended half-lives have the potential to improve adherence and outcomes in haemophilia beyond the results obtained with conventional rFVIII products. AIM: In the absence of head-to-head comparisons, annualized bleed rates (ABRs) and weekly factor consumption with rFVIII Fc fusion protein (rFVIIIFc) and conventional rFVIII products were indirectly compared using studies of continuous prophylaxis. METHODS: A systematic literature review was conducted to identify studies of rFVIII products for comparison with rFVIIIFc in the continuous prophylactic treatment of previously treated adolescents and adults with moderate and severe haemophilia A. Mean ABRs were compared between rFVIIIFc and individual rFVIII studies and between rFVIIIFc and a pooled measure for rFVIII estimated by meta-analysis. Comparisons of factor consumption were based on mean or median weekly factor consumption. RESULTS: Results from seven studies of conventional rFVIII products (injections 2-4 times week-1 ) were compared with rFVIIIFc (injections 1.4-2.4 times week-1 ). The pooled mean ABR for rFVIII products was significantly higher compared with rFVIIIFc (difference = 2.0; P = 0.007). Compared with most rFVIII studies, the reported weekly factor consumption was lower with rFVIIIFc [mean differences = 15.5-21.8 IU kg-1 week-1 (17-26%); median differences = 12.7-29.8 IU kg-1 week-1 (16-37%)]. In one comparison, mean weekly factor consumption with rFVIII was significantly lower but mean ABR was significantly higher than rFVIIIFc. CONCLUSION: Prophylaxis with rFVIIIFc may be associated with improved bleeding rates and lower weekly factor consumption than more frequently injected rFVIII products. Relative to rFVIII products with similar bleeding rates, results indicate that rFVIIIFc is associated with reduced weekly factor consumption while requiring fewer prescribed injections.
Authors: Amit Chhabra; Dean Spurden; Patrick F Fogarty; Bartholomew J Tortella; Emily Rubinstein; Simon Harris; Andreas M Pleil; Jennifer Mellor; Jonathan de Courcy; José Alvir Journal: Blood Coagul Fibrinolysis Date: 2020-04 Impact factor: 1.061
Authors: Johannes Oldenburg; Charles R M Hay; Víctor Jiménez-Yuste; Flora Peyvandi; Jean-François Schved; Johan Szamosi; Bent Winding; Stefan Lethagen Journal: BMJ Open Date: 2019-05-30 Impact factor: 2.692