A new population pharmacokinetic model for recombinant factor IX-Fc fusion concentrate including young children with haemophilia B.
Br J Clin Pharmacol
; 90(1): 220-231, 2024 01.
Article
em En
| MEDLINE
| ID: mdl-37567779
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator IX
/
Hemofilia B
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
/
Adult
/
Aged
/
Child
/
Child, preschool
/
Humans
/
Middle aged
Idioma:
En
Revista:
Br J Clin Pharmacol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Holanda