Pharmacometric analysis linking immunoglobulin exposure to clinical efficacy outcomes in chronic inflammatory demyelinating polyneuropathy

M.A. Tortorici; T. Yuraszeck; D. Cornblath; V. Bril; H.P. Hartung; G. Sobue; R.A. Lewis; I.S.J. Merkies; J.P. Lawo; M. Praus; B.L. Durn; O. Mielke; X.W. Ma; P. Jauslin; M. Pfister; I.N. Schaik; PATH Study Grp

doi:10.1002/psp4.12647

Pharmacometric analysis linking immunoglobulin exposure to clinical efficacy outcomes in chronic inflammatory demyelinating polyneuropathy

M.A. Tortorici^*, T. Yuraszeck, D. Cornblath, V. Bril, H.P. Hartung, G. Sobue, R.A. Lewis, I.S.J. Merkies, J.P. Lawo, M. Praus, B.L. Durn, O. Mielke, X.W. Ma, P. Jauslin, M. Pfister, I.N. Schaik, PATH Study Grp

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

The two main objectives of this analysis were to (i) characterize the relationship between immunoglobulin (Ig) exposure and chronic inflammatory demyelinating polyneuropathy (CIDP) disease severity using data from 171 patients with CIDP who received either subcutaneous Ig (IgPro20; Hizentra(R)) or placebo (PATH study), and to (ii) simulate and compare exposure coverage with various dosing approaches considering weekly dosing to be the reference dose. IgG pharmacokinetic (PK) parameters, including those from a previous population PK model, were used to predict individual IgG profile and exposure metrics. Treatment-related changes in Inflammatory Neuropathy Cause and Treatment (INCAT) scores were best described by a maximum effect (E-max) model as a function of Delta IgG (total serum IgG at INCAT score assessment minus baseline IgG levels before intravenous Ig restabilization). Simulations indicate that flexible dosing from daily to biweekly (every other week) provide an exposure coverage equivalent to that of a weekly Ig dose.

Original language	English
Pages (from-to)	839-850
Number of pages	12
Journal	CPT: Pharmacometrics and Systems Pharmacology
Volume	10
Issue number	8
DOIs	https://doi.org/10.1002/psp4.12647
Publication status	Published - 1 Aug 2021

Keywords

SUBCUTANEOUS IMMUNOGLOBULIN

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Cite this

Tortorici, M. A., Yuraszeck, T., Cornblath, D., Bril, V., Hartung, H. P., Sobue, G., Lewis, R. A., Merkies, I. S. J., Lawo, J. P., Praus, M., Durn, B. L., Mielke, O., Ma, X. W., Jauslin, P., Pfister, M., Schaik, I. N., & PATH Study Grp (2021). Pharmacometric analysis linking immunoglobulin exposure to clinical efficacy outcomes in chronic inflammatory demyelinating polyneuropathy. CPT: Pharmacometrics and Systems Pharmacology, 10(8), 839-850. https://doi.org/10.1002/psp4.12647

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abstract = "The two main objectives of this analysis were to (i) characterize the relationship between immunoglobulin (Ig) exposure and chronic inflammatory demyelinating polyneuropathy (CIDP) disease severity using data from 171 patients with CIDP who received either subcutaneous Ig (IgPro20; Hizentra(R)) or placebo (PATH study), and to (ii) simulate and compare exposure coverage with various dosing approaches considering weekly dosing to be the reference dose. IgG pharmacokinetic (PK) parameters, including those from a previous population PK model, were used to predict individual IgG profile and exposure metrics. Treatment-related changes in Inflammatory Neuropathy Cause and Treatment (INCAT) scores were best described by a maximum effect (E-max) model as a function of Delta IgG (total serum IgG at INCAT score assessment minus baseline IgG levels before intravenous Ig restabilization). Simulations indicate that flexible dosing from daily to biweekly (every other week) provide an exposure coverage equivalent to that of a weekly Ig dose.",

keywords = "SUBCUTANEOUS IMMUNOGLOBULIN",

author = "M.A. Tortorici and T. Yuraszeck and D. Cornblath and V. Bril and H.P. Hartung and G. Sobue and R.A. Lewis and I.S.J. Merkies and J.P. Lawo and M. Praus and B.L. Durn and O. Mielke and X.W. Ma and P. Jauslin and M. Pfister and I.N. Schaik and {PATH Study Grp}",

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Tortorici, MA, Yuraszeck, T, Cornblath, D, Bril, V, Hartung, HP, Sobue, G, Lewis, RA, Merkies, ISJ, Lawo, JP, Praus, M, Durn, BL, Mielke, O, Ma, XW, Jauslin, P, Pfister, M, Schaik, IN & PATH Study Grp 2021, 'Pharmacometric analysis linking immunoglobulin exposure to clinical efficacy outcomes in chronic inflammatory demyelinating polyneuropathy', CPT: Pharmacometrics and Systems Pharmacology, vol. 10, no. 8, pp. 839-850. https://doi.org/10.1002/psp4.12647

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AU - Tortorici, M.A.

AU - Yuraszeck, T.

AU - Cornblath, D.

AU - Bril, V.

AU - Hartung, H.P.

AU - Sobue, G.

AU - Lewis, R.A.

AU - Merkies, I.S.J.

AU - Lawo, J.P.

AU - Praus, M.

AU - Durn, B.L.

AU - Mielke, O.

AU - Ma, X.W.

AU - Jauslin, P.

AU - Pfister, M.

AU - Schaik, I.N.

AU - PATH Study Grp

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AB - The two main objectives of this analysis were to (i) characterize the relationship between immunoglobulin (Ig) exposure and chronic inflammatory demyelinating polyneuropathy (CIDP) disease severity using data from 171 patients with CIDP who received either subcutaneous Ig (IgPro20; Hizentra(R)) or placebo (PATH study), and to (ii) simulate and compare exposure coverage with various dosing approaches considering weekly dosing to be the reference dose. IgG pharmacokinetic (PK) parameters, including those from a previous population PK model, were used to predict individual IgG profile and exposure metrics. Treatment-related changes in Inflammatory Neuropathy Cause and Treatment (INCAT) scores were best described by a maximum effect (E-max) model as a function of Delta IgG (total serum IgG at INCAT score assessment minus baseline IgG levels before intravenous Ig restabilization). Simulations indicate that flexible dosing from daily to biweekly (every other week) provide an exposure coverage equivalent to that of a weekly Ig dose.

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