Exposure-response model of subcutaneous C1-inhibitor concentrate to estimate the risk of attacks in patients with hereditary angioedema

Ying Zhang, Michael A. Tortorici, DIpti Pawaskar, Ingo Pragst, Thomas MacHnig, Matthew Hutmacher, Bruce Zuraw, Marco Cicardi, Timothy Craig, Hilary Longhurst, Jagdev Sidhu

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Subcutaneous C1-inhibitor (HAEGARDA, CSL Behring), is a US Food and Drug Administration (FDA)-approved, highly concentrated formulation of a plasma-derived C1-esterase inhibitor (C1-INH), which, in the phase III Clinical Studies for Optimal Management in Preventing Angioedema with Low-Volume Subcutaneous C1-inhibitor Replacement Therapy (COMPACT) trial, reduced the incidence of hereditary angioedema (HAE) attacks when given prophylactically. Data from the COMPACT trial were used to develop a repeated time-to-event model to characterize the timing and frequency of HAE attacks as a function of C1-INH activity, and then develop an exposure-response model to assess the relationship between C1-INH functional activity levels (C1-INH(f)) and the risk of an attack. The C1-INH(f) values of 33.1%, 40.3%, and 63.1% were predicted to correspond with 50%, 70%, and 90% reductions in the HAE attack risk, respectively, relative to no therapy. Based on trough C1-INH(f) values for the 40 IU/kg (40.2%) and 60 IU/kg (48.0%) C1-INH (SC) doses, the model predicted that 50% and 67% of the population, respectively, would see at least a 70% decrease in the risk of an attack.

Original languageEnglish (US)
Pages (from-to)158-165
Number of pages8
JournalCPT: Pharmacometrics and Systems Pharmacology
Volume7
Issue number3
DOIs
StatePublished - Mar 2018

Fingerprint

Complement C1 Inhibitor Protein
Hereditary Angioedemas
Inhibitor
Attack
Estimate
Model
Therapy
Angioedema
United States Food and Drug Administration
Esterases
Relative Risk
Replacement
Plasmas
Timing
Dose
Incidence
Drugs
Plasma
Therapeutics
Decrease

All Science Journal Classification (ASJC) codes

  • Modeling and Simulation
  • Pharmacology (medical)

Cite this

Zhang, Ying ; Tortorici, Michael A. ; Pawaskar, DIpti ; Pragst, Ingo ; MacHnig, Thomas ; Hutmacher, Matthew ; Zuraw, Bruce ; Cicardi, Marco ; Craig, Timothy ; Longhurst, Hilary ; Sidhu, Jagdev. / Exposure-response model of subcutaneous C1-inhibitor concentrate to estimate the risk of attacks in patients with hereditary angioedema. In: CPT: Pharmacometrics and Systems Pharmacology. 2018 ; Vol. 7, No. 3. pp. 158-165.
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abstract = "Subcutaneous C1-inhibitor (HAEGARDA, CSL Behring), is a US Food and Drug Administration (FDA)-approved, highly concentrated formulation of a plasma-derived C1-esterase inhibitor (C1-INH), which, in the phase III Clinical Studies for Optimal Management in Preventing Angioedema with Low-Volume Subcutaneous C1-inhibitor Replacement Therapy (COMPACT) trial, reduced the incidence of hereditary angioedema (HAE) attacks when given prophylactically. Data from the COMPACT trial were used to develop a repeated time-to-event model to characterize the timing and frequency of HAE attacks as a function of C1-INH activity, and then develop an exposure-response model to assess the relationship between C1-INH functional activity levels (C1-INH(f)) and the risk of an attack. The C1-INH(f) values of 33.1{\%}, 40.3{\%}, and 63.1{\%} were predicted to correspond with 50{\%}, 70{\%}, and 90{\%} reductions in the HAE attack risk, respectively, relative to no therapy. Based on trough C1-INH(f) values for the 40 IU/kg (40.2{\%}) and 60 IU/kg (48.0{\%}) C1-INH (SC) doses, the model predicted that 50{\%} and 67{\%} of the population, respectively, would see at least a 70{\%} decrease in the risk of an attack.",
author = "Ying Zhang and Tortorici, {Michael A.} and DIpti Pawaskar and Ingo Pragst and Thomas MacHnig and Matthew Hutmacher and Bruce Zuraw and Marco Cicardi and Timothy Craig and Hilary Longhurst and Jagdev Sidhu",
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Zhang, Y, Tortorici, MA, Pawaskar, DI, Pragst, I, MacHnig, T, Hutmacher, M, Zuraw, B, Cicardi, M, Craig, T, Longhurst, H & Sidhu, J 2018, 'Exposure-response model of subcutaneous C1-inhibitor concentrate to estimate the risk of attacks in patients with hereditary angioedema', CPT: Pharmacometrics and Systems Pharmacology, vol. 7, no. 3, pp. 158-165. https://doi.org/10.1002/psp4.12271

Exposure-response model of subcutaneous C1-inhibitor concentrate to estimate the risk of attacks in patients with hereditary angioedema. / Zhang, Ying; Tortorici, Michael A.; Pawaskar, DIpti; Pragst, Ingo; MacHnig, Thomas; Hutmacher, Matthew; Zuraw, Bruce; Cicardi, Marco; Craig, Timothy; Longhurst, Hilary; Sidhu, Jagdev.

In: CPT: Pharmacometrics and Systems Pharmacology, Vol. 7, No. 3, 03.2018, p. 158-165.

Research output: Contribution to journalArticle

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T1 - Exposure-response model of subcutaneous C1-inhibitor concentrate to estimate the risk of attacks in patients with hereditary angioedema

AU - Zhang, Ying

AU - Tortorici, Michael A.

AU - Pawaskar, DIpti

AU - Pragst, Ingo

AU - MacHnig, Thomas

AU - Hutmacher, Matthew

AU - Zuraw, Bruce

AU - Cicardi, Marco

AU - Craig, Timothy

AU - Longhurst, Hilary

AU - Sidhu, Jagdev

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