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As the most commonly used FVIII concentrate in China, the individualized pharmacokinetics (PK) and clinical outcomes of Kovaltry (BAY81-8973) are not fully investigated in this population. Pediatric patients with severe hemophilia A were enrolled in Beijing Children's Hospital. After a three-day washout, they received PK tests after a single-dose infusion of 50 IU/kg. The blood samples were collected with a six-point assay. One-stage-based activated partial thromboplastin time was used for FVIII activity. The PK parameters were generated by WinNonlin software. The bleeding rates were calculated by their routine therapy record. The ultrasound was used to evaluate their both sides of knees, elbows and ankles. Sixty-one boys with severe hemophilia A were enrolled and their median age was 5.73 years. Twenty-nine of them were blood group-O. Compared with blood group-O patients, those non-O patients showed longer t 1/2 (15.26 vs. 13.03 h, P < 0.001) and reduced CL (3.04 vs. 3.66 mL/kg/h, P < 0.05). Patients with higher VWF:Ag level had longer half-life time (t 1/2) (r = 0.60, P < 0.0001) and lower clearance (CL) (r = −0.45, P < 0.001). Patients with higher trough level showed decreased bleeding rates compared with those owning a trough level below 1 IU/dL (P < 0.05). In general, the zero bleeding rates raised with elevation of trough level. However, 20–30% of patients with low trough level (<1 IU/dL) also showed no bleeds and 10–20% of patients with high trough level (>5 IU/dL) still suffer bleeds. An inconsistency of 28% between joint bleeds and ultrasound evaluation was showed. This study revealed the great inter-individual variability in PK parameters, clinical bleeding phenotype and joint vulnerability, which all should be considered in treating hemophilia A. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]