PK-tailored tertiary prophylaxis in patients with severe hemophilia A at beijing Children’s Hospital

摘要

Importance:Tertiary prophylaxis using a low-dose regimen is usually insufficient to prevent recurrent joint bleeding and deterioration in joint diseases in children with severe hemophilia A.Pharmacokinetic(PK)dosing is a useful approach to increase the precision and efficiency of prophylaxis.Objective:To explore the efficacy of PK-tailored tertiary prophylaxis in children with severe hemophilia A.Methods:We implemented a PK-tailored tertiary prophylaxis program for 15 boys with severe hemophilia A aged 5-16 years at Beijing Children’s Hospital.Following PK testing and a 6-month evaluation period(phase I),15 patients were divided in two groups according to individual PK data and actual bleeding:(1)a PK-tailored group[modified prophylaxis regimen according to PK data for the next 6 months(phase II);n=8]and(2)a maintenance group(continued the original regimen for the next 6 months;n=7).We compared the bleeding rate,infusion frequency,and factor VIII(FVIII)consumption between the two groups.results:In the PK-tailored group,the median annual joint bleeding rate was reduced from 7.8 in phase I to 1.4 in phase II,mean annual total factor consumption increased from 1619.0 IU/kg in phase I to 2401.9 IU/kg in phase II,and median infusion frequency for prophylaxis increased from 104 times/year in phase I to 156 times/year in phase II(P<0.05).Although the FVIII consumption increased,it remained at approximately half of the standard method.Interpretation:PK-tailored prophylaxis may represent a more efficient approach to individual prophylaxis in China,but further studies are required to verify this.