PB0175 - Impact of reagent on the estimation of Eloctate and Adynovate pharmacokinetic (PK) parameters?

Background: Laboratory reagents impact measured activity of extended half-life Factor VIII products (Peyvandi et al.). Potential over/under estimation of pharmacokinetic (PK) parameters, and consequently clinical judgement, can result from this variability. Since 2020, the Web-Accessible Population Pharmacokinetic Service – Hemophilia (WAPPS-Hemo) has been collecting reagent information when users submit PK studies for estimation of their PK parameters.

Aims: Explore the impact of laboratory one-stage reagents on Eloctate and Adynovate PK profiling.

Methods: Bayesian estimations used Population PK models developed by WAPPS-Hemo that included fat-free mass and age as covariates (Hajducek et al.). Logarithmic deviations from typical values predicted by the Population PK model (named etas) were calculated to provide metrics that aimed at removing the impact of known covariates on PK variability. The impact of each reagent/reagent type (Table 1) on the distribution of half-life deviations was assessed using Wilcoxon test (p-value < 0.05) comparing the half-lives from the reagent to the half-lives from all the remaining PK studies.

Results: In total, 2698 and 893 PK studies were available for Eloctate and Adynovate respectively, including 1541 and 372 with known reagent. Age ranged from 0.3 to 92 years (median:22.3) for Eloctate and from 0.7 to 77 (median:17.9) for Adynovate. Table 1 summarizes the terminal half-life values and deviations sorted by reagent and reagent type. Wilcoxon tests were only significant for the following reagents: Dade Actin FS (median:0.06, p=0.001) and Pathromtin SL (median:0.03, p=0.006) on Adynovate; and Pathromtin SL on Eloctate (median:-0.05, p=0.024).

Conclusion(s): Reagent type did not significantly impact the Bayesian estimation of Eloctate and Adynovate. Dade Actin FS and Pathromtin SL led to estimated half-lives 6% and 3% higher on average for Adynovate; and Pathromtin SL led to estimated half-lives 5% lower on average for Eloctate. However, such differences may not be clinically significant.

Acknowledgments: The IPSG provided financial support to this project.