Abstract Number: PB0845
Meeting: ISTH 2020 Congress
Background: Monitoring of Haemophilia A therapy includes the accurate determination of factor VIII activity (FVIII:C) with specific assays. Importantly, the results obtained in different assays can alter depending on the methodology, drug-type, assay conditions, phenotype and severity of disease. Therefore, individualized therapy through model-informed prediction of pharmacokinetic parameters (i.e. time above target (TaT)) can be challenging, if assay discrepancies are insufficiently accounted for.
Aims: Comparison of the prediction of the time above target in Hemophilia A patients with a published population pharmacokinetic model using two FVIII assays.
Methods: Pre-dose FVIII:C and five post-dose samples (0.25-48 h) of 35 patients receiving a B-domain deleted (BDD) or a full-length product were measured on an ACL TOP in a chromogenic assay (CSA) using BIOPHEN FVIII kit and a one-stage APTT assay (OSA), with HemoSil SynthaSil APTT reagent, respectively.
Secondly, the most accurate population pharmacokinetic model identified in a previous study (PAGE 28 (2019) Abstract 8970) was used to forecast TaT (FVIII:C>2 IU/dL) by supplying a previous trough concentration measured with either the CSA or OSA.
Results: For BDD the OSA was lower by 4 % (mean, 36 %SD) when compared to CSA, and for full-length products, the OSA was 6 % higher (mean, 34 %SD). A concentration dependency in both drug-types was observed, where CSA was higher than OSA at higher concentrations and vice versa at smaller concentrations.
The predicted TaT varied substantially among the two assays with differences larger than 12 h in 26% of the patients (Figure 1, red lines). While predictions in patients receiving the BDD product were in good alignment (Figure 1, dotted lines), predictions in full-length patients were mostly larger using OSA measurements.
Conclusions: Both assays can be used to predict the TaT in patients receiving the BDD product, while further improvements are needed in patients receiving a full-length product.
To cite this abstract in AMA style:Uster DW, Garcia CD, Riddell A, Aradom E, Musarara M, Hamid C, Tait C, Mangles S, Curry N, Chowdary P, Wicha SG. Differences in the Prediction of the Time above Target in Hemophilia A Patients Using a Chromogenic Assay and a One-stage Assay in Model-informed Precision Dosing [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/differences-in-the-prediction-of-the-time-above-target-in-hemophilia-a-patients-using-a-chromogenic-assay-and-a-one-stage-assay-in-model-informed-precision-dosing/. Accessed January 23, 2022.
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