Comparative pharmacokinetics of two extended half-life FVIII concentrates (Eloctate and Adynovate) in adolescents with hemophilia A: Is there a difference?

Manuel D Carcao; Pierre Chelle; Emily Clarke; Lussia Kim; Laura Tiseo; Massimo Morfini; Taneya Hossain; Margaret L Rand; Christine Brown; Andrea N Edginton; David Lillicrap; Alfonso Iorio; Victor S Blanchette

doi:10.1111/jth.14469

Comparative pharmacokinetics of two extended half-life FVIII concentrates (Eloctate and Adynovate) in adolescents with hemophilia A: Is there a difference?

J Thromb Haemost. 2019 Jul;17(7):1085-1096. doi: 10.1111/jth.14469. Epub 2019 Jun 2.

Authors

Manuel D Carcao¹, Pierre Chelle², Emily Clarke³, Lussia Kim⁴, Laura Tiseo⁴, Massimo Morfini⁵, Taneya Hossain⁶, Margaret L Rand^{7

8}, Christine Brown⁹, Andrea N Edginton², David Lillicrap⁹, Alfonso Iorio^{10

11}, Victor S Blanchette¹

Affiliations

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.

PMID: 31038793
DOI: 10.1111/jth.14469

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.

Keywords: adolescents; comparative; extended half-life; half-life; hemophilia; pharmacokinetics.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

ABO Blood-Group System
Adolescent
Child
Drug Substitution
Factor VIII / administration & dosage
Factor VIII / pharmacokinetics*
Half-Life
Hemophilia A / blood
Hemophilia A / diagnosis
Hemophilia A / drug therapy*
Hemostatics / administration & dosage
Hemostatics / pharmacokinetics*
Humans
Immunoglobulin Fc Fragments / administration & dosage
Male
Metabolic Clearance Rate
Ontario
Recombinant Fusion Proteins / administration & dosage
Recombinant Fusion Proteins / pharmacokinetics*
Severity of Illness Index
von Willebrand Factor / metabolism

Substances

ABO Blood-Group System
Hemostatics
Immunoglobulin Fc Fragments
Recombinant Fusion Proteins
factor VIII-Fc fusion protein
von Willebrand Factor
BAX 855
Factor VIII