In:
British Journal of Clinical Pharmacology, Wiley
Abstract:
Recombinant factor IX Fc fusion protein (rFIX‐Fc) is an extended half‐life factor concentrate administered to haemophilia B patients. So far, a population pharmacokinetic (PK) model has only been published for patients aged ≥12 years. The aim was to externally evaluate the predictive performance of the published rFIX‐Fc population PK model for patients of all ages and develop a model that describes rFIX‐Fc PK using real‐world data. Methods We collected prospective and retrospective data from patients with haemophilia B treated with rFIX‐Fc and included in the OPTI‐CLOT TARGET study (NTR7523) or United Kindom (UK)‐EHL Outcomes Registry (NCT02938156). Predictive performance was assessed by comparing predicted with observed FIX activity levels. A new population PK model was constructed using nonlinear mixed‐effects modelling. Results Real‐world data were obtained from 37 patients (median age: 16 years, range 2–71) of whom 14 were aged 〈 12 years. Observed FIX activity levels were significantly higher than levels predicted using the published model, with a median prediction error of −48.8%. The new model showed a lower median prediction error (3.4%) and better described rFIX‐Fc PK, especially for children aged 〈 12 years. In the new model, an increase in age was correlated with a decrease in clearance ( P 〈 .01). Conclusions The published population PK model significantly underpredicted FIX activity levels. The new model better describes rFIX‐Fc PK, especially for children aged 〈 12 years. This study underlines the necessity to strive for representative population PK models, thereby avoiding extrapolation outside the studied population.
Type of Medium:
Online Resource
ISSN:
0306-5251
,
1365-2125
Language:
English
Publisher:
Wiley
Publication Date:
2023
detail.hit.zdb_id:
1498142-7
SSG:
15,3