Abstract
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.