A new population pharmacokinetic model for recombinant factor IX‐Fc fusion concentrate including young children with haemophilia B

Koopman, Sjoerd F., Goedhart, Tine M.H.J., Bukkems, Laura H., Mulders, Trevor M., Leebeek, Frank W.G., Fijnvandraat, Karin, Coppens, Michiel, Mathias, Mary, Collins, Peter W. ORCID: https://orcid.org/0000-0002-6410-1324, Tait, R. Campbell, Bagot, Catherine N., Curry, Nicola, Payne, Jeanette, Chowdary, Pratima, Cnossen, Marjon H., Mathôt, Ron A.A. and for the OPTI‐CLOT study group and SYMPHONY consortium 2024. A new population pharmacokinetic model for recombinant factor IX‐Fc fusion concentrate including young children with haemophilia B. British Journal of Clinical Pharmacology 90 (1) , pp. 220-231. 10.1111/bcp.15881

PDF - Published Version Available under License Creative Commons Attribution Non-commercial. Download (1MB)

Abstract

Aims: 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by-nc/4.0/
Publisher:	Wiley
ISSN:	0306-5251
Date of First Compliant Deposit:	13 September 2023
Date of Acceptance:	27 July 2023
Last Modified:	17 Jan 2024 13:22
URI:	https://orca.cardiff.ac.uk/id/eprint/162469

Actions (repository staff only)

Edit Item