Dose tailoring of human cell line-derived recombinant factor VIII simoctocog alfa: using a limited sampling strategy in patients with severe haemophilia A.

BACKGROUND: The use of www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2607 prophylaxis in haemophilia A is considered the standard of care, particularly in children. Despite adjustment of doses for body weight and/or age, a large pharmacokinetic (PK) variability between patients has been observed. PK-tailored prophylaxis may help clinicians adjust coagulation factor FVIII activity (FVIII:C) to the desired level, which may differ in individual patients.

OBJECTIVES: To develop a population PK model for simoctocog alfa based on pooled clinical trial data and to develop a Bayesian estimator to allow PK parameters in individual patients to be estimated using a reduced number of blood samples.

PATIENTS/METHODS: PK data from 86 adults and 29 children/adolescents with severe haemophilia A were analyzed. The Factor VIII data measured using two different assays (chromogenic and the one-stage clotting assay) were fit to separate develop population PK models using nonlinear mixed-effect models. A Bayesian estimator was then developed to estimate the time above the threshold of 1%.

RESULTS: The PK data for chromogenic and the one-stage clotting assays were both best described by a 2-compartment models. Simulations demonstrated good predictive capacity. The limited sampling strategy using blood sample at 3 and 24 h allowed an accurate estimation of the time above the threshold of 1% FVIII:C (mean bias 0.01 and 0.11, mean precision 0.18 and 0.45 for two assay methods).

CONCLUSION: In this study, we demonstrated that a Bayesian approach can help to reduce the number of samples required to estimate the time above the threshold of 1% FVIII:C with good accuracy.