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Clinical Validation of Population Pharmacokinetic Model for Plasma-Derived Factor VIII/VWF Comparing 3 Years Follow-up

1Hospital Universitari i Politecnic La Fe, Pharmacy Department and Haemostasis and Thrombosis Unit, Valencia, Spain, 2Hospital Universitari i Politecnic La Fe, Haemostasis and Thrombosis Unit, Valencia, Spain, 3Hospital Universitari i Politecnic La Fe, Pharmacy Department, Valencia, Spain, 4Universidad de Valencia, Department of Physiotherapy, Valencia, Spain

Abstract Number: PB0996

Meeting: ISTH 2020 Congress

Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical

Background: Individual pharmacokinetic profiling (iPK) in hemophilia A (HA) has become a useful tool to individualize prophylaxis using population PK models (PopPK). Recently a specific PopPK for plasma-derived factor VIII/VWF (pdFVIII/VWF) has been developed with WAPPS-Hemo.

Aims: Validate in clinical practice the novel Bayesian model for pdFVIII/VWF.

Methods: Prospective study in HA severe/moderate patients in prophylaxis with pdFVIII/VWF (Fanhdi®) comparing three periods of 1 year: standard prophylaxis (1P, 2016), early PK adoption (2P, 2017), and PK-guided prophylaxis (3P, 2018). PK parameters analyzed with WAPPS-Hemo were: half-life (t1/2); trough level at 24, 48 and 72 h (TL24, TL48, TL72); and time to reach FVIII levels of 1, 2, 5% (T1%, T2%, T5%). Clinical variables included were: age, dose/kg, consumption, annualized joint bleeding rate (AJBR) and number of joint spontaneous and provoked bleeds. Wilcoxon and Kruskal Wallis tests (SPSS®) were used to compare the PK parameters and clinical variables between periods.

Results: Thirty patients were analyzed, 28 had severe HA and 2 moderate HA. Mean age was 31.2 years (range=12.4-50.8). Eleven patients adjusted prophylaxis according PK and weight gain (10 increased dose or frequency and 1 patient reduced dose).
After PK-guided prophylaxis (3P), patients with joint bleeds were related to lower age, t1/2, TL48, TL72 and T5% compared to patients with zero AJBR ( Table 1). No differences in AJBR were observed comparing 1P and 2P, whereas a trend to higher consumption was reported (Table 2). However, after PK-guided prophylaxis (P1 vs P3) lower spontaneous joint bleeds and a trend lower AJBR were reported, but no differences in consumption (Table 2).

Conclusions: PK-guided prophylaxis allows the individualization of treatment, as well as improvements in bleeding control, especially in younger patients with short t1/2. Collaborative projects as WAPPS-Hemo allow the development of specific PopPK for clotting factors without published PopPK.

PK parameters & clinical variables Zero joint bleeds. Median Zero joint bleeds. IQR Joint bleeds ≥1. Median Joint bleeds ≥1. IQR P-value
Age (years) 40.5 20-52.5 8 4-32 0.016
Weight (kg) 62.5 58.5-69 32 23-72 0.134
t1/2 (h) 15.4 12.8-19.4 10.6 9.0-14.8 0.008
TL24 (IU/dL) 16.3 13.8-24.3 11.6 9.1-20.2 0.061
TL48 (IU/dL) 6.0 4.0-9.9 3.3 2.2-5.3 0.011
TL72 (IU/dL) 2.3 1.5-5.5 1.5 0.7-1.9 0.014
T5% (h) 52.1 43.6-74.8 40.0 33.8-49.5 0.016
T2%* (h) 71.5 57.3-86.0 61.0 49.3-70.0 0.061
T1%* (h) 93.1 90.0-144.0 84.7 63.0-101.5 0.084

[Table 1. Analysis of joint bleeding causes using a specific pdFVIII/VWF PopPK (PK-guided tailoring period; 3P 2018).]

Clinical variables 1P. Median 1p. IQR 2P. Median 2P. IQR 3P. Median 3P. IQR P-value 1P vs 2P P-value 1P vs 3P
Dose (IU)/kg/week 60.6 49.3-94.60 62.7 47.5-94.0 76.7 55.6-99.4 0.49 0.12
Consumption/kg (UI/kg) 3039.47 2573.2-4741.0 3436.6 2702.7-4959.5 3219.9 2605.0-4991.0 0.09 0.14
AJBR 0.0 0.0-2.0 0.0 0.0-1.0 0.0 0.0-1.0 1.00 0.09
Spontaneous joint bleeds 0.0 0.0-1.0 0.0 0.0-1.0 0.0 0.0-0.0 0.76 0.01
Provoked joint bleeds 0.0 0.0-0.0 1.0 1.0-1.0 0.0 0.0-1.0 0.43 0.48

[Table 2. Comparisons between consumption and joint bleeding rates using Kruskal-Wallis test periods of PK study (1P 2016 vs. 2P 2017; and 1P 2016 vs.]

To cite this abstract in AMA style:

Megías-Vericat JE, Bonanad S, Haya S, Cid AR, Marqués MR, Monte-Boquet E, Pérez-Alenda S, Bosch P, Querol F, Poveda JL. Clinical Validation of Population Pharmacokinetic Model for Plasma-Derived Factor VIII/VWF Comparing 3 Years Follow-up [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/clinical-validation-of-population-pharmacokinetic-model-for-plasma-derived-factor-viii-vwf-comparing-3-years-follow-up/. Accessed September 27, 2023.

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