Clinical outcomes in hemophilia A patients undergoing tailoring of prophylaxis based on population-based pharmacokinetic dosing

Published:November 15, 2018DOI:


      • PK based tailoring of prophylaxis in hemophilia was proposed to 39 Japanese patients.
      • Dose increase, infusion frequency reduction, or switch to extended half-life concentrates can explain.
      • Adherence to treatment improved or did not change.
      • The annualized bleeding improved or remained unchanged, and was associated with time spent above 0.01 or 0.05 IU/mL.



      Standard prophylaxis dosing based on bodyweight may result in over- or under-dosing due to interpatient variability. Adopting individual pharmacokinetic (PK) based tailoring may improve adherence to treatment guideline, and consequently clinical outcomes. Here we report clinical observations performed across the adoption of individual PK based tailoring in a single center in Japan.


      An individual PK study on sparse samples was modeled on myPKFiT or WAPPS-Hemo, depending on concentrate, and used to optimize treatment regimens. Adherence to prophylaxis and bleeding rate were calculated from patient diaries. Radiological joint scores were used to assess arthropathy, and SPSS to perform all the analyses.


      Thirty-nine patients underwent PK profiling, and 20 required and accepted a modification of their treatment (8 increases in dose, 5 reductions in frequency, 5 switches to extended half-life (EHL)). Adherence to prophylaxis remained the same in those increasing the dose, whilst increased in all the other groups. Annualized bleeding rate (ABR) and annualized joint bleeding rate (AjBR) decreased in all the groups but reached statistical significance only in those switched to EHL and showed a larger reduction in those patients without baseline arthropathy. Longer time spent above a 1% or 5% threshold was associated with a decrease in the ABR/AjBR.


      Our study results suggest that PopPK based tailoring supported changing treatment regimen in nearly half of the patients, and may have contributed to an improvement in the adherence and a reduction in the ABR/AjBR.


      PK (pharmacokinetic), SHL (standard half-life products), EHL (extended half-life products), rFVIII (recombinant factor VIII), FVIII:C (FVIII activity), ABR (annualized bleeding rate), AjBR (annualized joint bleeding rate)


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