OC 27.3 - Individualized target trough FVIII level and optimized prophylaxis in pediatric patients with hemophilia A

Background: Prophylaxis is the standard treatment for hemophilia A(HA). Considering the inter-individual variability of pharmacokinetics (PK), bleeding phenotype and joint vulnerability, an individualized prophylactic protocol is vital to optimizing the therapy of HA.

Aims: To investigate the clinical outcomes of the new proposed PK-guided dosing strategy which combined the comprehensive evaluation system for escalation.

Methods: Patients with severe HA and without FVIII inhibitors were enrolled. After a 72h washout period and a single-dose infusion of 50IU/kg of their routine used FVIII concentrate, each one received a PK test with a five-point design. The trough levels were calculated by WAPPS-Hemo. The bleeding rates (ABR, annualized bleeding rate; AJBR, annualized joint bleeding rate) were estimated from six months before enrollment to the study exit. The ultrasound and HJHS were used to evaluate the patients’ joints (both sides of ankles, knees, and elbows) every 12 months. The escalation criteria depended on joint bleeds, US scores and HJHS scores. Their quality of life was assessed by CHOKLAT sheets.

Results: Fifty-eight severe HA boys who had an observational period of over 2 years were analyzed. Their age and body weight was 5.3(2.8,6.9)years and 21.5(16,25)kg respectively. At baseline, 34 of them had a trough level of < 1IU/dL and seven target joints were detected according to the previous definition. During the study period, 47 escalations were observed. Joint bleeds count the most proportion (48.3%,N=28). Significantly reduced ABR [0(0,6)vs.4(0,8),P < 0.0001] and AJBR[0(0,0.25)vs.0(0,2),P < 0.0001] was observed at study exit as well as the trend of decreased bleeding rates as the study progressed. Also,85% (6/7) of the target joints vanished during the study. Statistical improvement of US scores(P=0.04) and HJHS scores(P=0.02) was also reported at the study exit.

Conclusion(s): This newly proposed PK-guided dosing strategy could reduce bleeding rates, eliminate target joints and improve impaired joints, which could be an optimal individualized prophylactic protocol.