TY - JOUR
T1 - Predictive performance of pharmacokinetic-guided prophylactic dosing of factor concentrates in hemophilia A and B
AU - Goedhart, Tine M.H.J.
AU - Bukkems, Laura H.
AU - Zwagemaker, Anne Fleur
AU - Coppens, Michiel
AU - Fijnvandraat, Karin
AU - Schols, Saskia E.M.
AU - Schutgens, Roger E.G.
AU - Eikenboom, Jeroen
AU - Heubel-Moenen, Floor C.J.I.
AU - Ypma, Paula F.
AU - Nieuwenhuizen, Laurens
AU - Meijer, Karina
AU - Leebeek, Frank W.G.
AU - Mathôt, Ron A.A.
AU - Cnossen, Marjon H.
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/3
Y1 - 2024/3
N2 - Background: Pharmacokinetic (PK)-guided dosing is used to individualize factor (F)VIII and FIX replacement therapy. Objectives: This study investigates the reliability and feasibility of PK-guided prophylactic dosing of factor concentrates in hemophilia A and B. Methods: In this multicenter, prospective cohort study, people of all ages with hemophilia received prophylactic treatment with factor concentrates based on individual PK parameters. During follow-up, at least 4 measured FVIII/FIX levels per patient were compared with corresponding predicted levels obtained by Bayesian forecasting. Predictive performance was defined as adequate when ≥80% of measured FVIII/FIX levels were within ±25% of prediction (relative error). Additionally, mean absolute error and mean error were calculated. In post hoc analyses, predictive performance was assessed allowing maximum absolute errors of 1 (trough), 5 (mid), and 15 (peak) IU/dL. Five-point scale questionnaires addressed feasibility of PK guidance. Results: We included 50 patients (median age, 19 years; range: 2-72 years). Median follow-up was 36 weeks. Seventy-one percent of levels (58% trough, 83% mid, and 80% peak) were within ±25% of prediction. Mean absolute errors were 0.8 (trough), 2.0 (mid), and 8.6 (peak) IU/dL. In post hoc analyses, 81% (trough), 96% (mid), and 82% (peak) of levels were within set limits. Patients reported low burden and high satisfaction. Conclusion: PK-guided dosing was reliable according to post hoc analyses, based on low absolute errors that were regarded as clinically irrelevant in most cases. The predefined predictive performance was achieved in mid and peak factor levels but not in trough factor levels due to measurement inaccuracy. PK guidance also seemed feasible.
AB - Background: Pharmacokinetic (PK)-guided dosing is used to individualize factor (F)VIII and FIX replacement therapy. Objectives: This study investigates the reliability and feasibility of PK-guided prophylactic dosing of factor concentrates in hemophilia A and B. Methods: In this multicenter, prospective cohort study, people of all ages with hemophilia received prophylactic treatment with factor concentrates based on individual PK parameters. During follow-up, at least 4 measured FVIII/FIX levels per patient were compared with corresponding predicted levels obtained by Bayesian forecasting. Predictive performance was defined as adequate when ≥80% of measured FVIII/FIX levels were within ±25% of prediction (relative error). Additionally, mean absolute error and mean error were calculated. In post hoc analyses, predictive performance was assessed allowing maximum absolute errors of 1 (trough), 5 (mid), and 15 (peak) IU/dL. Five-point scale questionnaires addressed feasibility of PK guidance. Results: We included 50 patients (median age, 19 years; range: 2-72 years). Median follow-up was 36 weeks. Seventy-one percent of levels (58% trough, 83% mid, and 80% peak) were within ±25% of prediction. Mean absolute errors were 0.8 (trough), 2.0 (mid), and 8.6 (peak) IU/dL. In post hoc analyses, 81% (trough), 96% (mid), and 82% (peak) of levels were within set limits. Patients reported low burden and high satisfaction. Conclusion: PK-guided dosing was reliable according to post hoc analyses, based on low absolute errors that were regarded as clinically irrelevant in most cases. The predefined predictive performance was achieved in mid and peak factor levels but not in trough factor levels due to measurement inaccuracy. PK guidance also seemed feasible.
KW - factor IX
KW - factor VIII
KW - hemophilia A
KW - hemophilia B
KW - pharmacokinetics
KW - preventive medicine
UR - http://www.scopus.com/inward/record.url?scp=85190957882&partnerID=8YFLogxK
U2 - 10.1016/j.rpth.2024.102397
DO - 10.1016/j.rpth.2024.102397
M3 - Article
AN - SCOPUS:85190957882
SN - 2475-0379
VL - 8
JO - Research and practice in thrombosis and haemostasis
JF - Research and practice in thrombosis and haemostasis
IS - 3
M1 - 102397
ER -