Background: Kovaltry (BAY81-8973) is an unmodified full-length factor VIII (FVIII) concentrate that enhances the pharmacokinetic (PK) profiles as compared to some other standard half-life time FVIII concentrates. However, the PK of Kovaltry in haemophiliac patients aged <12 years has not been reported previously.
Aim: To investigate the pharmacokinetics and clinical outcomes of Kovaltry in 35 paediatric patients aged <12 years.
Methods: A total of 35 boys with severe haemophilia A were enrolled from August 2019 to May 2020 in Beijing Children's Hospital. After 72-hour washout, PK tests were performed post-infusion of 50 IU/kg Kovaltry in a five-timepoint assay. WinNonlin software was used to generate individual PK parameters. The dose, frequency and bleeding details were collected within the first 6 months after switching to Kovaltry from other FVIII concentrates.
Results: Compared to the blood group O, patients with blood group non-O showed longer mean half-life (t1/2 ) (p < .01), lower mean clearance (CL) (p = .01) and similar in vivo recovery (IVR) (p = .51). Higher von Willebrand factor antigen (VWF:Ag) level was correlated to longer t1/2 (p < .0001) and lower CL (p < .01). IVR was correlated to body mass index (BMI) (p < .0001). Patients with trough level >3 IU/dL demonstrated lower annual bleeding rate (ABR) (p < .01), annual joint bleeding rate (AJBR) (p < .01) and annual spontaneous bleeding rate (ASBR) (p < .01).
Conclusion: This study firstly reported the PK profiles of Kovaltry in 35 paediatric patients <12 years old. The great inter-individual variability of PK parameters was also confirmed in these patients. VWF:Ag and blood group were major influencing factors of t1/2 and CL of Kovaltry, while BMI was a vital predictor for IVR. Patients with high trough FVIII level in routine prophylaxis had reduced bleeding rates.
Keywords: factor Ⅷ; haemophilia A; haemorrhage; paediatrics; pharmacokinetics.
© 2021 John Wiley & Sons Ltd.