pharmacokinetics of recombinant human C1 esterase inhibitor in children with hereditary angioedema
Siobhán Hayes et al. Ann Allergy Asthma Immunol. 2021.
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Abstract
Background: Recombinant human C1 esterase inhibitor (rhC1-INH) is indicated in the United States for the treatment of acute HAE attacks in adolescents and adults; it is also indicated in Europe for children aged 2 years and older. A need exists for further insight into potential pharmacokinetic (PK) differences in functional C1-INH levels by age (ie, children, adolescents, and adults).
Objective: To employ population PK modeling to predict C1-INH levels following rhC1INH administration.
Methods: Data from a phase 2 pediatric trial (children aged 4-13 years at screening) were added to a database of 6 trials in adults/adolescents. An unpublished population PK model was refined and used to simulate C1-INH exposure.
Results: Analysis included 153 individuals (14 healthy volunteers; 139 patients with HAE) and 1788 functional C1-INH measurements (59 from 20 patients in the pediatric trial). Bodyweight (population weight, 16-128 kg) was a key predictor of C1-INH volume of distribution. Age was not a predictor of C1-INH PK after inclusion of bodyweight in the model. Simulations of the recommended rhC1-INH dosing regimen (bodyweight <84 kg, 50 U/kg; =84 kg, 4200 U) showed that overall C1-INH exposure was comparable among age groups. Predicted peak functional C1-INH concentrations were at/above the lower level of normal (=0.7 U/mL) for 99.8% of adults (=18 years), 99.8% of adolescents (14-17 years), and 96.0% of children (2-13 years).
Conclusion: Analyses support the same weight-based rhC1-INH dosing for HAE attacks in children as currently recommended for adolescents/adults. These results support clinical trial data, which demonstrated similar safety and efficacy profiles across these age groups.
Keywords: C1 esterase inhibitor; Ruconest; complement C1 inhibitor protein; hereditary angioedema; pharmacokinetics; recombinant C1 esterase inhibitor.
Copyright © 2021. Published by Elsevier Inc.
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