Improved clinical outcome after PK-Guided Personalised Prophylaxis with my-PKFIT® in patients with hemophilia A without inhibitors

Abstract

Objective: Prophylaxis is the gold standard in patients with severe hemophilia. In recent years, personalisation of prophylaxis treatment according to pharmacokinetic properties has been used in treatment. In this study, personalisation treatment experience based on the pharmacokinetic dosing tool my-PKfit results in pediatric and adult patients from three centers is shared. Material and Methods: myPKfit (www1.mypkfit.com) was used to evaluate pharmacokinetic parameters in hemophilia A patients receiving recombinant Factor VIII (Takeda Advate ®) prophylaxis. 75 samples in 34 patients (3 samples in 7 patients, 2 samples in 27 patients) were analysed for pharmacokinetic evaluation. Age, weight and baseline FVIII level of the patients were recorded. Pharmacokinetic curves were obtained after entering sampling times, factor dose and sample results. The annual bleeding rate (ABR) of the patients were evaluated before and after the changes made after the pharmacokinetic evaluation. Results: The median age of 34 patients with severe hemophilia A without inhibitors was 12.3±8.7 (1.5-37) years, and the mean weight was 40.0±22.0 (10-83) kg. All patients had a baseline FVIII level of less than or equal to 2 IU/dl. All patients were receiving primary or secondary/tertiary prophylaxis. The mean half-life of the factors of the patients was 9.6±1.4 (7.0-13.4) hours, and the mean time reached below 1 IU/dl was 48.9±11.2 (16.0-77.0) hours. Prophylactic factor therapy was changed in 17 patients after myPKfit, dose increased in 9 patients, the frequency increased in 6 patients, and both dose and frequency increased in 2 patients. With a mean follow-up period of 23.7 +16 (2-49) months, in 17 patients whose prophylaxis regimen was changed after the PK evaluation by myPkyfit, ABR was found to be significantly lower in the post-change period, compared to the last one year before the change of regimen (2.94 + 2.19 and 0.58 + 1.00 respectively) P: 0.028. Discussion: A pharmacokinetic study by the Bayesian method is an increasingly used method for personalised prophylaxis regimen. We believe that myPKfit is beneficial in providing effective and appropriate prophylaxis.