ISTH Congress Abstracts

Official abstracts site for the ISTH Congress

MENU 

Predictive performance of pharmacokinetic-guided prophylactic dosing of factor concentrates in hemophilia A and B (OPTI-CLOT TARGET study) – Preliminary results

1Erasmus MC Sophia Children’s Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands, Rotterdam, Zuid-Holland, Netherlands, 2Department of Clinical Pharmacology - Hospital Pharmacy, Amsterdam UMC, University of Amsterdam, Amsterdam, Amsterdam, Noord-Holland, Netherlands, 3Amsterdam University Medical Centers, Amsterdam, the Netherlands, Amsterdam, Noord-Holland, Netherlands, 4Department of Pediatric Hematology, Emma Children’s Hospital, Amsterdam University Medical Centers, location AMC, University of Amsterdam, Amsterdam, the Netherlands; Department of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands, Amsterdam, Noord-Holland, Netherlands, 5Department of Hematology, Radboud university medical center, Nijmegen, the Netherlands; Hemophilia Treatment Center Nijmegen-Eindhoven-Maastricht, the Netherlands, Nijmegen, Gelderland, Netherlands, 6University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands, Utrecht, Utrecht, Netherlands, 7Department of Internal Medicine, Division of Thrombosis and Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands., Leiden, Zuid-Holland, Netherlands, 8Department of Hematology, Maastricht University Medical Center, Maastricht, the Netherlands, Maastricht, Limburg, Netherlands, 9Department of Hematology, Haga Hospital, The Hague, Netherlands, The Hague, Zuid-Holland, Netherlands, 10Department of Hematology, Máxima Medical Center, Eindhoven, Netherlands; Radboud university medical center, Hemophilia Treatment Center, Nijmegen – Eindhoven – Maastricht, Netherlands, Eindhoven, Noord-Brabant, Netherlands, 11University Medical Center Groningen, Groningen, Groningen, Netherlands, 12Department of Hematology, Erasmus MC, University Medical Center Rotterdam, The Netherlands, Rotterdam, Zuid-Holland, Netherlands, 13Department of Hospital Pharmacy, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands, Amsterdam, Noord-Holland, Netherlands, 14Department of Pediatric Hematology, Sophia Children’s Hospital, Erasmus University Medical Center, Erasmus University Rotterdam, Rotterdam, The Netherlands, Rotterdam, Zuid-Holland, Netherlands

Abstract Number: OC 27.5

Meeting: ISTH 2022 Congress

Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical

Background: Pharmacokinetic(PK)-guided dosing is used to individualize factor VIII (FVIII) and factor IX (FIX) therapy.

Aims: Investigate the predictive performance of PK-guided prophylactic dosing of factor concentrates in hemophilia patients.

Methods: In this multicenter, prospective cohort study, hemophilia patients of all ages on prophylaxis with standard half-life (SHL) and extended half-life (EHL) factor concentrates received PK-guided dosing. Treating physicians set individual target levels based on previous FVIII/FIX levels, physical activities and bleeding phenotype. During 9 months follow-up, at least four measured FVIII/FIX levels per patient were compared to corresponding predictions obtained by Bayesian forecasting. Predictive performance was adequate when ≥80% of the measured FVIII/FIX levels were within ±25% of the prediction. Bias and accuracy were calculated using mean error (ME) and mean absolute error (MAE), respectively. During post-hoc analysis, predictive performance was assessed allowing maximal difference of 1 (trough), 5 (mid) and 15 (peak) IU/dL. Ethical approval and informed consent was obtained.

Results: Fifty patients were included (Table 1). Twenty-seven patients completed the study (January, 2022). Median targeted FVIII/FIX trough level under PK-guidance was 2 IU/dL [IQR 1-4]. Predictive performance of 189 levels is shown in Figure 1. Sixty-six percent of levels (54% trough, 77% mid, 72% peak) were within ±25% of prediction. MAE was 0.7 (trough), 2.6 (mid) and 10.5 (peak) IU/dL. According to post-hoc analysis, 77% (trough), 92% (mid) and 78% (peak) of levels were within set limits. Patients who completed the study had a median number of total and spontaneous bleeds of one (IQR 0-3) and zero (IQR 0-1), respectively.

Conclusion(s): The prespecified predictive performance target was not achieved, partly due to high measurement error especially in trough levels. In our opinion, the predictive performance of PK-guidance in clinical practice is better represented by post-hoc analysis, the ME and MAE. These low errors were regarded as clinically irrelevant in most cases.

To cite this abstract in AMA style:

Goedhart T, Bukkems L, Coppens M, Fijnvandraat K, Schols S, Schutgens R, Eikenboom J, Heubel-Moenen F, Ypma P, Nieuwenhuizen L, Meijer K, Leebeek F, Mathôt R, Cnossen M. Predictive performance of pharmacokinetic-guided prophylactic dosing of factor concentrates in hemophilia A and B (OPTI-CLOT TARGET study) – Preliminary results [abstract]. https://abstracts.isth.org/abstract/predictive-performance-of-pharmacokinetic-guided-prophylactic-dosing-of-factor-concentrates-in-hemophilia-a-and-b-opti-clot-target-study-preliminary-results/. Accessed October 2, 2023.

« Back to ISTH 2022 Congress

ISTH Congress Abstracts - https://abstracts.isth.org/abstract/predictive-performance-of-pharmacokinetic-guided-prophylactic-dosing-of-factor-concentrates-in-hemophilia-a-and-b-opti-clot-target-study-preliminary-results/