Manuel D Carcao1, Pierre Chelle2, Emily Clarke3, Lussia Kim4, Laura Tiseo4, Massimo Morfini5, Taneya Hossain6, Margaret L Rand7,8, Christine Brown9, Andrea N Edginton2, David Lillicrap9, Alfonso Iorio10,11, Victor S Blanchette1. 1. Division of Haematology/Oncology, Department of Paediatrics and Child Health Evaluative Sciences, Research Institute, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. 2. School of Pharmacy, University of Waterloo, Waterloo, ON, Canada. 3. Department of Nursing, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. 4. Child Health Evaluative Sciences, Research Institute, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. 5. Italian Association of Haemophilia Centers, Florence, Italy. 6. Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, ON, Canada. 7. Division of Haematology/Oncology, Department of Paediatrics and Translational Medicine, Research Institute, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. 8. Departments of Laboratory Medicine & Pathobiology and Biochemistry, University of Toronto, Toronto, ON, Canada. 9. Department of Pathology & Molecular Medicine, Queen's University, Kingston, ON, Canada. 10. McMaster-Bayer Endowed Research Chair for Clinical Epidemiology of Congenital Bleeding Disorders, Department of Medicine, McMaster University, Hamilton, ON, Canada. 11. Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.
Abstract
Essentials The PK parameters of Eloctate vs Adynovate were compared using one-stage and chromogenic assays in 25 boys (12-18 years). The FVIII levels were taken at 3, 24, 48, and 72 hours following a dose of either FVIII; levels analyzed by WAPPS PK program. The PK profiles (half-life, clearance, and time to 5%, 3%, and 1%) were not statistically different for the two EHL FVIIIs. The significant interpatient variability in PK is mainly related to VWF levels (and blood group). BACKGROUND: A head-to-head comparison of the pharmokinetcs (PK) of extended half-life (EHL) factor VIII (FVIII) concentrates in the same subjects has not been reported. Recently, boys (ages 12-18 years) with hemophilia A in Canada were required to switch from Eloctate to Adynovate. OBJECTIVES: Compare the PK profiles of Eloctate vs Adynovate in the same boys. METHODS: Boys switching from Eloctate to Adynovate prophylaxis had FVIII levels sampled at 3, 24, 48, and 72 hours following a regular prophylactic infusion of Eloctate and then 1-3 months later, of Adynovate. Testing was done by one-stage assay (OSA) and chromogenic assay (CA). The PK parameters were determined with the Web Accessible Population Pharmacokinetic Service (WAPPS)-Hemo PK tool. RESULTS: Twenty-five boys (mean age 15.3 years; range: 12.1-18.4; 9 O blood group) underwent switching. Mean (range) terminal half-lives with the OSA were 16.1 hours (10.4 to 23.4; Eloctate) and 16.7 hours (11.0 to 23.6; Adynovate) (NS). With the CA, these were 18.0 hours (12.0 to 25.5; Eloctate) and 16.0 hours (10.3 to 22.9; Adynovate) (P = 0.001). There were no significant differences between the two EHL-FVIIIs in clearance, area under the concentration vs time curve (AUC), Vss, or time for FVIII levels to drop to 5%, 3%, and 1%. At the 72-h time point, mean observed FVIII levels following a mean dose of 39.3 IU/kg of Eloctate were 4.4% (OSA) and 4.4% (CA). For Adynovate, these were 5.1% (OSA) and 5.3% (CA) following similar doses. There was considerable interpatient variation in PK, mainly explained by differences in blood group/von Willebrand factor (VWF) levels. CONCLUSIONS: Eloctate and Adynovate have almost identical PK parameters. When switching from one to another no prophylaxis regimen change is needed.
Essentials The PK parameters of Eloctate vs Adynovate were compared using one-stage and chromogenic assays in 25 boys (12-18 years). The FVIII levels were taken at 3, 24, 48, and 72 hours following a dose of either FVIII; levels analyzed by WAPPS PK program. The PK profiles (half-life, clearance, and time to 5%, 3%, and 1%) were not statistically different for the two EHL FVIIIs. The significant interpatient variability in PK is mainly related to VWF levels (and blood group). BACKGROUND: A head-to-head comparison of the pharmokinetcs (PK) of extended half-life (EHL) factor VIII (FVIII) concentrates in the same subjects has not been reported. Recently, boys (ages 12-18 years) with hemophilia A in Canada were required to switch from Eloctate to Adynovate. OBJECTIVES: Compare the PK profiles of Eloctate vs Adynovate in the same boys. METHODS:Boys switching from Eloctate to Adynovate prophylaxis had FVIII levels sampled at 3, 24, 48, and 72 hours following a regular prophylactic infusion of Eloctate and then 1-3 months later, of Adynovate. Testing was done by one-stage assay (OSA) and chromogenic assay (CA). The PK parameters were determined with the Web Accessible Population Pharmacokinetic Service (WAPPS)-Hemo PK tool. RESULTS: Twenty-five boys (mean age 15.3 years; range: 12.1-18.4; 9 O blood group) underwent switching. Mean (range) terminal half-lives with the OSA were 16.1 hours (10.4 to 23.4; Eloctate) and 16.7 hours (11.0 to 23.6; Adynovate) (NS). With the CA, these were 18.0 hours (12.0 to 25.5; Eloctate) and 16.0 hours (10.3 to 22.9; Adynovate) (P = 0.001). There were no significant differences between the two EHL-FVIIIs in clearance, area under the concentration vs time curve (AUC), Vss, or time for FVIII levels to drop to 5%, 3%, and 1%. At the 72-h time point, mean observed FVIII levels following a mean dose of 39.3 IU/kg of Eloctate were 4.4% (OSA) and 4.4% (CA). For Adynovate, these were 5.1% (OSA) and 5.3% (CA) following similar doses. There was considerable interpatient variation in PK, mainly explained by differences in blood group/von Willebrand factor (VWF) levels. CONCLUSIONS: Eloctate and Adynovate have almost identical PK parameters. When switching from one to another no prophylaxis regimen change is needed.
Authors: Victor S Blanchette; Laura Zunino; Viviane Grassmann; Chris Barnes; Manuel D Carcao; Julie Curtin; Shannon Jackson; Liane Khoo; Vladimir Komrska; David Lillicrap; Massimo Morfini; Gabriela Romanova; Derek Stephens; Ester Zapotocka; Margaret L Rand; Jan Blatny Journal: Thromb Haemost Date: 2021-04-14 Impact factor: 6.681