OC 73.4 - Personalized treatment by pharmacokinetic-guided dosing in von Willebrand disease; A prospective multicenter study, OPTI-CLOT/To WiN study

Wednesday, June 26, 2024

11:00 – 11:15 ICT

Room: Ballroom B4

Co-Author(s)

WA

Wala Al Arashi

MD
Department of Pediatric Hematology and Oncology, Erasmus MC Sophia Children’s Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
MC

Michael E. Cloesmeijer

MSc
Department of Hospital Pharmacy and Clinical Pharmacology, Amsterdam UMC – location AMC, The Netherlands
Amsterdam, Noord-Holland, Netherlands
Frank W.G Leebeek, MD PhD

Internist-hematologist, Professor
Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
LN

Laurens Nieuwenhuizen

MD
Department of Hematology, Maxima Medisch Centrum, Eindhoven, The Netherlands
Eindhoven, Noord-Brabant, Netherlands
Floor Heubel-Moenen

MD, PhD
Department of Hematology, Maastricht University Medical Center, Maastricht, The Netherlands
Maastricht, Limburg, Netherlands
Karina Meijer

MD, PhD, professor
Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Groningen, Groningen, Netherlands
RM

Ron A.A. Mathôt

PhamdD, PhD,
Department of Hospital Pharmacy and Clinical Pharmacology, Amsterdam UMC – location AMC, The Netherlands
Amsterdam, Noord-Holland, Netherlands
MC

Marjon H. Cnossen

MD, PhD, professor
Department of Pediatric Hematology and Oncology, Erasmus MC Sophia Children’s Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands

Presenting Author(s)

Caroline Mussert, MD

PhD candidate
Department of hematology – pediatric hematology, Erasmus Medical Center Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, the Netherlands
Rotterdam, Zuid-Holland, Netherlands

Background: It is well known that there is substantial interindividual pharmacokinetic (PK) variation in Von Willebrand factor(VWF)/factor VIII(FVIII) concentrates. This variation is not reduced when dosing patients according to bodyweight, as previously reported by Hazendonk et al.

Aims: We aimed to investigate the reliability of PK-guided dosing of VWF/FVIII concentrates (Haemate P®) in Von Willebrand disease (VWD).

Methods: A multicenter, single arm, intervention study was conducted. Patients with VWD requiring Haemate P® to prevent bleeding during a medical intervention from April 8th 2019 until July 1st 2023 were selected. Dosing regimens based on individual PK parameters were calculated using the population PK-model by Bukkems et. al. Predicted and measured VWF activity (VWF:Act) and FVIII(FVIII:C) levels were compared to assess predictive performance applying median absolute error(MAE).

Results: Twenty-nine VWD patients were included: 11 type 1 and 18 type 2 (Table 1). Overall, predefined targets were achieved (Figure 1,boxplot A/B). On day of medical intervention, one patient had a VWF:Act peak level below the predefined target (0.42 instead of >0.5 IU/mL). Seven of 55 VWF:Act trough levels (13%) were below the predefined target levels during treatment (range:0.01-0.13 IU/mL lower). Figure 1, boxplots C/D, demonstrate the predictive performance. On the intervention day, VWF:Act peak levels were slightly higher than predicted (MAE was 0.075[IQR:0.011-0.28] IU/mL) and VWF:Act trough levels were slightly lower (MAE was -0.047[IQR:-0.08-0.011] IU/mL). After the first day of intervention until end of treatment, VWF:Act trough levels were higher than predicted (MAE:0.067-0.24 IU/mL). FVIII levels were all higher than predicted (MAE:0.14-0.46 IU/mL).

Conclusion(s): Predictive performance of PK-guided dosing of Haemate P® in VWD is adequate as MAE of VWF:Act is low. Moreover, achievement of VWF:Act target levels is more optimal compared to bodyweight-based dosing. However, due to the heterogeneity of VWD, obtaining more is essential to further establish optimal, personalized treatment by PK-guided dosing of VWF/FVIII concentrates.