Abstract Number: OC 27.5
Meeting: ISTH 2022 Congress
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.
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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/