Azusa Nagao1, Cindy H T Yeung2, Federico Germini3, Takashi Suzuki4. 1. Department of Blood Coagulation, Ogikubo Hospital, Tokyo, Japan. Electronic address: azusa_nagao@ogikubo-hospital.or.jp. 2. Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada. 3. Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada; Department of Health Sciences, Università degli Studi di Milano, Milan, Italy. 4. Department of Blood Coagulation, Ogikubo Hospital, Tokyo, Japan.
Abstract
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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