Pharmacokinetic-guided prophylaxis improved clinical outcomes in paediatric patients with severe haemophilia A.

Background: The traditional weight-based dosing regimen can lead to under- or overdosage due to the interindividual variability of pharmacokinetic (PK) parameters. PK-guided prophylaxis can be an optimized therapy choice.

Aim: This study aimed to investigate the clinical outcomes of PK-guided prophylaxis in 46 boys with severe haemophilia A.

Methods: Forty-six boys with severe haemophilia A were enrolled in Beijing Children's Hospital. The PK tests were performed using a five-point assay. PK parameters were calculated using WinNonlin software. The dosing regimen and bleeding rates recorded during the observation period. The adjustment was based on PK evaluation, bleeding details, doctor's advice and patients' choice.

Results: The half-life time, in vivo recovery and clearance of Kovaltry were 14.34 ± 2.68 h, 1.78 ± 0.29 kg/dl and 3.38 ± 0.94 ml/kg/h, respectively. In 18 patients without any change in the dosing regimen, the trough level was 4.0 ± 2.41 IU/dl and the bleeding rates were similar after PK tests. For patients with a higher trough level after adjustment, higher dose and frequency were observed, as well as a higher trough level. Also, reduced annual bleeding rate (ABR), annual joint bleeding rate and annual spontaneous bleeding rate (ASBR) were found. In five patients with a reduced trough level, lower infusion frequency and weekly coagulation factor VIII (FVIII) consumption were observed, with no statistically significant difference in ABR and ASBR.

Conclusion: PK-guided prophylaxis can help haemophiliac patients improve quality of life by decreasing bleeds with appropriate FVIII consumption and reducing infusion frequency without increments in bleeds, thus optimizing haemophilia treatment.