Prophylaxis Dose Adjustment in Hemophilia a Using a New Version of Population Pharmacokinetics Estimation Model Based on Bayesian Procedure
Authors: Sánchez-Raga José María , Santandreu Estelrich Maria Margalida , Galmés Sureda Bernat , Massanet Antonio Palomero , Puget Guiomar , Sampol Antonia , Canaro Mariana 
Published: October 2019

Abstract
INTRODUCTION
Prophylaxis with factor VIII (FVIII) is considered the gold standard for managing hemophilia A (HA) patients without inhibitors to prevent bleedings and to preserve normal musculoskeletal function. Classically, the prophylaxis with a standard half-life FVIII is 20 to 40 IU/kg administered every other day. In practice this "one-size-fits-all" way of dosing does not work in many patients due to the interindividual variability on the concentration-time profile of FVIII, body weight, age, blood group and level of Von Willebrand factor.
Pharmacokinetic (PK)-guided regimens have been proposed as an effective way to optimize prophylaxis efficacy. Different online PK tools have been developed to estimate patients' PK with only 2 blood samples. The integration of PK and clinical data can help physicians to adjust dosing.
Since 2014 we have been using an online tool to perform PK estimation in patients using the FVIII product Advate® (myPKFiT®, www.mypkfit.com; Baxter Healthcare Corporation; Haemophilia 2014, 20 (Suppl.2):15). In June 2018 a new version has been launch, the version 3.0. This v3.0 includes a dose calculation update based on the ability to modify an individual dose or trough level of an individual prophylaxis regimen providing an accurate adjustment of prophylaxis dosing in comparison with version 2.0 (v2.0).
This report describes the impact of the PK estimation in the infusion frequency and factor consumption, comparing both versions, in a cohort of people with HA.
METHODS
This is an observational case series from a single hemophilia treatment Spanish center. The inclusion criteria were: patients receiving prophylaxis with octocog alfa who accepted to participate in the PK study. Two blood samples have been collected for the estimation of FVIII PK (3-4 hours and 24-28 hours after administration of their usual dose of FVIII) in real world practice. We measured FVIII using one-stage assay. The FVIII trough levels were adjusted between 1% and 3% according to patients characteristics. Demographic data, PK parameters, infusion frequency, dosage and consumption after PK adjustment of prophylaxis using the v2.0 and v3.0 tool were analyzed.
RESULTS
Eleven patients were evaluated (7 severe, 3 moderate, 1 mild HA) aged 2-43 years (median 14 years). There were no differences in PK parameters between v2.0 and v3.0 as the applied algorithm for both versions is the same. PK results are shown in the Panel A of the table below. The elected trough level was between 1-3% depending of the physical activity and joint health of every individual patient. Prophylaxis regimen was modified in 6/11 patients after PK analysis with both versions of the App: 2 pediatric patients increased their FVIII dose and 3 adults increased their treatment frequency. We have only observed differences in 3 patients comparing the two versions: Patient 1 started a new infusion regimen (every 48h to 48-48-72h) with a mild increase in consumption, and patient 2 and 5 maintained the regimen every 48h with slight reductions in consumption. Results are shown in the Panel B of the table below.
CONCLUSIONS
Both versions of myPKFit™ are a helpful tool to adjust FVIII dosing regimens. This latest version allows to individualize even more the treatment regimen and to achieve a more efficient consumption. Prospective evaluation of the use of PK‐tailored prophylaxis in routine care and its impact on patient outcomes is needed.
Table. Table.

Disclosures
No relevant conflicts of interest to declare.