A Novel, Enriched Population Pharmacokinetic Model for Recombinant Factor VIII-Fc Fusion Protein Concentrate in Hemophilia A Patients

UK-EHL Outcomes Registry OPTI-CLOT, Laura H. Bukkems, Jessica M. Heijdra, Mary Mathias, Peter W. Collins, Charles R. M. Hay, Robert C. Tait, Sarah Mangles, Bethan Myers, G. Evans, Benjamin Bailiff, Nicola Curry, Jeanette Payne, Steve Austin, Tine M. H. J. Goedhart, Frank W. G. Leebeek, Karina Meijer, Karin Fijnvandraat, Pratima Chowdary, Ron A. A. Mathot*Marjon H. Cnossen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Background The currently published population pharmacokinetic (PK) models used for PK-guided dosing in hemophilia patients are based on clinical trial data and usually not externally validated in clinical practice. The aim of this study was to validate a published model for recombinant factor VIII-Fc fusion protein (rFVIII-Fc) concentrate and to develop an enriched model using independently collected clinical data if required.

Methods Clinical data from hemophilia A patients treated with rFVIII-Fc concentrate (Elocta) participating in the United Kingdom Extended Half-Life Outcomes Registry were collected. The predictive performance of the published model was assessed using mean percentage error (bias) and mean absolute percentage error (inaccuracy). An extended population PK model was developed using nonlinear mixed-effects modeling (NONMEM).

Results A total of 43 hemophilia A patients (FVIII

Conclusion We concluded that the existing rFVIII-Fc population PK model is valid for patients >= 12 years. However, it is not reliable in younger patients. Our alternative model, constructed from real world patient data including children, allows for better description of patients >= 5 years.

Original languageEnglish
Pages (from-to)747-757
Number of pages11
JournalThrombosis and Haemostasis
Issue number5
Publication statusPublished - 1-May-2020


  • recombinant factor VIII-Fc
  • population
  • pharmacokinetics
  • child
  • validation
  • AGE

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