Haemophilia : the official journal of the World Federation of Hemophilia · 2025
In Silico Assessment of Limited Blood Sampling Strategies for Individualised Pharmacokinetic-guided Dosing of Efanesoctocog Alfa in Haemophilia A Patients.
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den Hollander Jelien, Cnossen Marjon H, Mathôt Ron A A
Аннотация
INTRODUCTION: Efanesoctocog alfa is a novel factor VIII (FVIII) concentrate with a unique molecular design that enables Von Willebrand Factor-independent clearance in patients with haemophilia A. Limited sampling strategies (LSSs) are necessary to implement accurate pharmacokinetic (PK)-guided dosing for efanesoctocog alfa in clinical practice.
AIM: This in silico study aims to evaluate the predictive performance of 10 LSSs with one to three samples for estimating individual PK profiles of efanesoctocog alfa.
METHODS: Monte Carlo simulations based on a published population PK model generated individual FVIII activity-time profiles for a virtual population. LSSs were applied to sample from these profiles, and PK parameters, FVIII activity peak level at 0.5 h (C0.5), FVIII activity trough level at 168 h (C168) and time above FVIII activity thresholds (5, 10 and 40 IU/dL) were estimated using Bayesian forecasting.
RESULTS: All LSSs complied with our requirements of a relative mean prediction error of <±5% and a relative root mean square error of <25%. For prophylactic dosing advice, a LSS was considered clinically suitable if at least 80% of predicted C168 had a prediction error within -3 to 3 IU/dL. This criterion was met by one two-sample LSS and three three-sample LSSs. For pre-operative dosing advice, suitability required at least 80% of predicted C0.5 within -20 to 20 IU/dL, fulfilled by one two-sample and six three-sample LSSs.
CONCLUSIONS: Several LSSs demonstrated adequate predictive performance for PK-guided dosing of efanesoctocog alfa.
AIM: This in silico study aims to evaluate the predictive performance of 10 LSSs with one to three samples for estimating individual PK profiles of efanesoctocog alfa.
METHODS: Monte Carlo simulations based on a published population PK model generated individual FVIII activity-time profiles for a virtual population. LSSs were applied to sample from these profiles, and PK parameters, FVIII activity peak level at 0.5 h (C0.5), FVIII activity trough level at 168 h (C168) and time above FVIII activity thresholds (5, 10 and 40 IU/dL) were estimated using Bayesian forecasting.
RESULTS: All LSSs complied with our requirements of a relative mean prediction error of <±5% and a relative root mean square error of <25%. For prophylactic dosing advice, a LSS was considered clinically suitable if at least 80% of predicted C168 had a prediction error within -3 to 3 IU/dL. This criterion was met by one two-sample LSS and three three-sample LSSs. For pre-operative dosing advice, suitability required at least 80% of predicted C0.5 within -20 to 20 IU/dL, fulfilled by one two-sample and six three-sample LSSs.
CONCLUSIONS: Several LSSs demonstrated adequate predictive performance for PK-guided dosing of efanesoctocog alfa.