Details

Autor(en) / Beteiligte

• Goedhart, Tine M.H.J.
• Bukkems, Laura H.
• Zwagemaker, Anne-Fleur
• Coppens, Michiel
• Fijnvandraat, Karin
• Schols, Saskia E.M.
• Schutgens, Roger E.G.
• Eikenboom, Jeroen
• Heubel-Moenen, Floor C.J.I.
• Ypma, Paula F.
• Nieuwenhuizen, Laurens
• Meijer, Karina
• Leebeek, Frank W.G.
• Mathôt, Ron A.A.
• Cnossen, Marjon H.

Titel

Predictive performance of pharmacokinetic-guided prophylactic dosing of factor concentrates in hemophilia A and B

Ist Teil von

• Research and practice in thrombosis and haemostasis, 2024-03, Vol.8 (3), p.102397-102397, Article 102397

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2024

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Pharmacokinetic (PK)-guided dosing is used to individualize factor (F)VIII and FIX replacement therapy. This study investigates the reliability and feasibility of PK-guided prophylactic dosing of factor concentrates in hemophilia A and B. 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. 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. 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. •Pharmacokinetic (PK) guidance of prophylaxis in hemophilia is used but not adequately validated.•This prospective study investigates reliability and feasibility of PK guidance of prophylaxis.•PK guidance of prophylaxis is reliable based on its low absolute and relative errors.•Low burden and high satisfaction reported by patients and physicians suggest its feasibility.