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

Abstract

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.

Individualised prophylaxis based on personalised target trough FVIII level optimised clinical outcomes in paediatric patients with severe haemophilia A

“…Urgent request of a higher trough level was also revealed by the low zero bleeding proportions of different trough level groups at study entry. This was in accordance with other well conducted studies before 20,21 . During the individualised prophylaxis period, the most escalations (59.6%) were due to the joint bleeds alone.…”

“…This was in accordance with other well conducted studies before. 20 , 21 During the individualised prophylaxis period, the most escalations (59.6%) were due to the joint bleeds alone. But if joint bleed is the only criteria for escalation, dose adjustment would not have been performed in the remaining 40.6% in lack of systematical evaluation.…”

Pharmacokinetic profile of children with haemophilia A receiving low‐dose FVIII prophylaxis in Indonesia: A single centre experience

“…The substantial differences in PK profiles lead to FVIII dosing discrepancies compared with traditional fixed dosing regimens. 11,12,18,[23][24][25][26][27] The median t 1/2 observed in our study was similar to the half-life of Koate-DVI reported in the published data from Grifols (16.13 h). 28 The t 1/2 in our study would differ if a different concentrate was used.…”

“…This finding is similar to those of other studies that evaluated the PK profiles of HA patients on prophylaxis with a standard regimen or LDP of FVIII. The substantial differences in PK profiles lead to FVIII dosing discrepancies compared with traditional fixed dosing regimens 11,12,18,23–27 …”

Exploration of the minimum necessary FVIII level at different physical activity levels in pediatric patients with hemophilia A

“…PK analysis was performed by Web-Accessible Population Pharmacokinetic System (WAPPS-Hemo). A five-point assay was utilized (Pre-dose, 1 h, 9 h, 24 h, 48 h) (10). FVIII levels were determined by one-stage assay.…”