Extended half‐life factor VIII concentrates in adults with hemophilia A: Comparative pharmacokinetics of two products

摘要

Background The use of pharmacokinetic (PK) studies to help design personalized prophylaxis regimens for factor VIII (FVIII) concentrate in individuals with hemophilia A has been recognized for many years but only became practical for routine clinical use with the availability of web‐accessible population PK applications based on Bayesian analysis. Objective To compare PK variables using population PK studies done on 2 extended half‐life recombinant FVIII concentrates in 23 individuals with hemophilia A after switching from one product to the other. Methods We retrospectively analyzed PK parameters derived from the Web‐Accessible Population Pharmacokinetic Service‐Hemophilia (WAPPS‐HEMO) application on 23 individuals with severe or moderately severe hemophilia A who were required to switch from recombinant FVIII Fc (Eloctate; Biogen, Cambridge, MA, USA) to recombinant antihemophilic factor PEGylated (Adynovate; Takeda Pharmaceutical Company, Osaka, Japan) between 2016 and 2017. Results There were minor PK differences between Eloctate and Adynovate, but some parameters did reach statistical significance, namely in vivo recovery (mean, 2.73?IU/dL per IU/kg vs 2.41?IU/dL per IU/kg), clearance (mean, 0.163?mL/h vs 0.194?mL/h), and volume of distribution at steady state (mean, 42.5?ml/kg vs 49.8?mL/kg). Smaller nonsignificant trends toward higher values for Adynovate were seen in terminal half‐life, area under the curve, and predicted times to 5% and 1% residual FVIII after infusion. Conclusion Population PK analysis revealed differences between the two extended half‐life FVIII concentrates, reaching significance for in vivo recovery, clearance, and volume of distribution.