Comparison of single subject and population-based pharmacokinetics for optimizing prophylaxis with simoctocog alfa in patients with haemophilia A

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Introduction: The use of pharmacokinetic assessment for optimal prophylactic dosing of factor concentrates in haemophilia has gained increasing enthusiasm over the last decade. However, blood sampling on several occasions is burdensome and limited sampling using population-based PK is appealing. Aim: To compare the pharmacokinetics and dosing recommendations for prophylaxis using six-point single subject versus population-based method (WAPPS-Hemo) for simoctocog alfa (Nuwiq®). Methods: Twelve adult patients with severe haemophilia A received a factor VIII (FVIII) dose of ≈50 IU/kg, and the activity was measured pre-infusion and at 30 min, 6, 9, 24 and 48 h post-infusion. Half-life (t1/2), weight-normalized AUC and time to troughs of 5%, 3% and 1% were calculated. The correlation between the PK algorithms was assessed using intraclass correlations (ICC) and dosing estimations were provided. Results: WAPPS-Hemo yielded a slightly longer mean t1/2, but the overall correlation between the methods was good (ICC ≥0.79) The time to troughs of 5%, 3% and 1% showed ICCs ≥0.86. For all variables, the most converging limited time point was 6+48 h. Additional time points did not improve the correlation. Despite similar pharmacokinetics, the mean estimated dose for a specific trough level varied from 60% less to 20% more using the population-based approach. The time to 1% and the corresponding dose was sensitive to the baseline assumption. Conclusion: Our data support the use of population-based PK for patients on simoctocog alfa prophylaxis but also indicates differences, stressing the importance of the sampling scheme and monitoring actual FVIII levels achieved.


  • Jan Astermark
  • Anna Olsson
  • Pierre Chelle
  • Kinga Täckström
  • Maria Walger
  • Maria Magnusson
  • Alfonso Iorio
Enheter & grupper
Externa organisationer
  • Skåne University Hospital
  • Sahlgrenska University Hospital
  • University of Waterloo
  • Karolinska University Hospital
  • McMaster University
  • Octapharma Nordic AB

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Hematologi


StatusE-pub ahead of print - 2021 maj 9
Peer review utfördJa