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Pharmacokinetics and Associated Efficacy of Emicizumab in Humans: A Systematic Review

Donners, Anouk A. M. T., Rademaker, Carin M. A., Bevers, Lisanne A. H., Huitema, Alwin D. R., Schutgens, Roger E. G., Egberts, Toine C. G., Fischer, Kathelijn·2021·Clinical Pharmacokinetics
DOI 10.1007/s40262-021-01042-wPMC PMC8585815
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Fig. 1 Linear dose–concentration relationship of emicizumab in PwHA. The mean or median Ctrough,ss according to increasing doses of emicizumab per week (mg/kg/week). Q2W and Q4W intervals shown per week. Data from PwHA (n = 469) receiving multiple dose regimens were included (see footnote ‘a’ for 15 study subgroups, in electronic supplementary Table ST2). PwHA people with hemophilia A, Ctrough,ss trough plasma concentration in steady-state conditions, Q2W 2-weekly dose interval, Q4W 4-weekly dose interval
Fig. 1 Linear dose–concentration relationship of emicizumab in PwHA. The mean or median Ctrough,ss according to increasing doses of emicizumab per week (mg/kg/week). Q2W and Q4W intervals shown per week. Data from PwHA (n = 469) receiving multiple dose regimens were included (see footnote ‘a’ for 15 study subgroups, in electronic supplementary Table ST2). PwHA people with hemophilia A, Ctrough,ss trough plasma concentration in steady-state conditions, Q2W 2-weekly dose interval, Q4W 4-weekly dose intervalCC BY-NC · PubMed Central
Fig. 2 Trough concentrations of emicizumab with variability across various subgroups in PwHA. The weighted variability (%CV) of the Ctrough,ss of emicizumab was similar across FVIII inhibitor status and across various dosing intervals, whereas children had slightly less variability than adults/adolescents. The overall weighted %CV was 32%. Data from PwHA (n = 469) receiving multiple dose regimens were included (see footnote ‘a’ for 15 study subgroups, in electronic supplementary Table ST2). PwHA people with hemophilia A, %CV percentage coefficient of variation, Ctrough,ss trough plasma concentration in steady-state conditions, Q2W 2-weekly dose interval, Q4W 4-weekly dose interval
Fig. 2 Trough concentrations of emicizumab with variability across various subgroups in PwHA. The weighted variability (%CV) of the Ctrough,ss of emicizumab was similar across FVIII inhibitor status and across various dosing intervals, whereas children had slightly less variability than adults/adolescents. The overall weighted %CV was 32%. Data from PwHA (n = 469) receiving multiple dose regimens were included (see footnote ‘a’ for 15 study subgroups, in electronic supplementary Table ST2). PwHA people with hemophilia A, %CV percentage coefficient of variation, Ctrough,ss trough plasma concentration in steady-state conditions, Q2W 2-weekly dose interval, Q4W 4-weekly dose intervalCC BY-NC · PubMed Central
Fig. 3 Emax model with concentration–response relationship of emicizumab in PwHA. Fit of an Emax model of ABRs of treated bleeds according to the Ctrough,ss of emicizumab in PwHA (n = 349), described by ABR=ABRbaseline×(1-((Ctrough,ss×Emax)/(Ctrough,ss+EC50)). Included ABRs were model-based, estimated using negative binominal regression. The EC50 was estimated at 1.47 µg/mL (SE 0.90) and the effectiveness plateau was established. The dashed line is the 95% confidence interval, and symbol size equals study size. Data from PwHA receiving maintenance were included (see footnote ‘b’ for 11 study subgroups, in electronic supplementary Table ST2). Emax maximum effect, PwHA people with hemophilia A, ABRs annualized bleeding rates, Ctrough,ss trough plasma concentration in steady-state conditions, EC50 half maximal effective concentration, SE standard error
Fig. 3 Emax model with concentration–response relationship of emicizumab in PwHA. Fit of an Emax model of ABRs of treated bleeds according to the Ctrough,ss of emicizumab in PwHA (n = 349), described by ABR=ABRbaseline×(1-((Ctrough,ss×Emax)/(Ctrough,ss+EC50)). Included ABRs were model-based, estimated using negative binominal regression. The EC50 was estimated at 1.47 µg/mL (SE 0.90) and the effectiveness plateau was established. The dashed line is the 95% confidence interval, and symbol size equals study size. Data from PwHA receiving maintenance were included (see footnote ‘b’ for 11 study subgroups, in electronic supplementary Table ST2). Emax maximum effect, PwHA people with hemophilia A, ABRs annualized bleeding rates, Ctrough,ss trough plasma concentration in steady-state conditions, EC50 half maximal effective concentration, SE standard errorCC BY-NC · PubMed Central

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Cited by

Metadata

Authors
Donners, A. A. M. T., Rademaker, C. M. A., Bevers, L. A. H., Huitema, A. D. R., Schutgens, R. E. G., Egberts, T. C. G., & Fischer, K.
Venue
Clinical Pharmacokinetics
Publisher
Springer Science and Business Media LLC
Published
2021-08-13
Volume
60
Issue
11
Pages
1395-1406
ISSN
  • 0312-5963
  • 1179-1926
DOI
10.1007/s40262-021-01042-w
PMC
PMC8585815
Cited by
40
References
5
Language
en
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