Pharmacokinetics Using myPKFiTR for Personalized Prophylaxis in Children with Severe Hemophilia a.

Abstract

Prophylactic administration of factor VIII (FVIII) products is necessary to prevent bleeding and preserve normal musculoskeletal function in children with severe hemophilia A (HA). However, the pharmacokinetics (PK) of FVIII is considerable variation among children with HA. The regimen for prophylaxis should be individualized according to the age, bleeding phenotype, the presence of arthropathy, physical activity, and PK. The myPKFiTR has been developed as the device to personalize dosing with a 2 sample PK based on the population PK Bayesian tool. In this study we report our single-center experience to estimate PK profiles and to individualize dose and dosing interval based on myPKFiTR. Fifteen patients with severe HA aged from 1 to 25 years were enrolled in this study for personalized prophylaxis. The half-life of FVIII was significantly shorter in young children than that in adolescents. The half-lives in children less than 6 years of age were 6.5 to 8 hours, and 11 to 14 hours in adolescents, respectively. The clearance of FVIII was inversely correlated with the half-life of FVIII. FVIII trough levels were 2 to 4% in children less than 6 years of age. The prophylactic regimen in adolescents was individually determined according to the personal results of PK study and to patients' life style and activities. Adolescent patients actively participated in sports, such as table tennis, badminton, track and field, basketball, and football after school. The FVIII level after school was easily estimated by the use of myPKFiT according to the dose and duration of replacement. The doses of FVIII products were individually determined to have more than 10 to 30% of FVIII level at the time of sports activity. During personalized prophylaxis (12 to 24 months), more than 90% (14/15) of patients had no bleeds and 100% had no spontaneous bleeds. All patients did not have any bleeds during school life. Compared with the preceding standard prophylaxis period, the annual bleeding rates were significantly decreased in the phase of personalized prophylaxis. In our experience of use of myPKFiTR, these results suggest that the estimation of FVIII level may be useful for prophylaxis in patients with severe HA. Furthermore, utilization of simple PK study has the benefit for improvement of adherence and concordance, provision of patients' and their guardians' education as well as personalized prophylaxis. Recently, half-life extended FVIII concentrates have been utilized in HA patients. The immediate development of PK study tool should be necessary to estimate individual FVIII PK for new FVIII products. DisclosuresNo relevant conflicts of interest to declare.