Population-based exposure-efficacy modeling of ustekinumab in patients with moderate to severe plaque psoriasis
Ustekinumab, a human immunoglobulin G1 kappa (IgG1k) monoclonal antibody that binds with high affinity to human interleukin-12 and interleukin-23, has demonstrated efficacy in patients with psoriasis. The objective of this study was to perform exposure-response modeling to increase the understanding of reduction in disease severity following treatment with ustekinumab in patients with moderate to severe psoriasis who participate in two phase III studies (PHOENIX 1 and PHOENIX 2). Patients were randomly assigned to receive ustekinumab 45 mg or 90 mg (n = 1312; 11,624 Psoriasis Area and Severity Index [PASI] scores) or placebo (n = 665; 3278 PASI scores). Disease severity was assessed using PASI scores. A population mechanism-based exposure-response model of ustekinumab using NONMEM was developed using serum ustekinumab concentrations and PASI scores. The pharmacodynamic response effect was the reduction in PASI score. The placebo effect, although minor, was also integrated into the model. None of the covariate factors evaluated (eg, demographics, baseline disease characteristics, comorbidities) significantly contributed to the between-subject variability in the pharmacodynamic parameters. The developed exposure-response model can serve as a basis to support future alternative dosing regimens for ustekinumab in patients with moderate to severe plaque psoriasis. A robust exposure-response relationship has been confirmed for ustekinumab in psoriasis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2010 |
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| Erschienen: |
2010 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:50 |
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| Enthalten in: |
Journal of clinical pharmacology - 50(2010), 3 vom: 21. März, Seite 257-67 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhou, Honghui [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.05.2010 Date Revised 19.11.2015 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1177/0091270009343695 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM193021137 |
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| 100 | 1 | |a Zhou, Honghui |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Population-based exposure-efficacy modeling of ustekinumab in patients with moderate to severe plaque psoriasis |
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| 500 | |a Date Revised 19.11.2015 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Ustekinumab, a human immunoglobulin G1 kappa (IgG1k) monoclonal antibody that binds with high affinity to human interleukin-12 and interleukin-23, has demonstrated efficacy in patients with psoriasis. The objective of this study was to perform exposure-response modeling to increase the understanding of reduction in disease severity following treatment with ustekinumab in patients with moderate to severe psoriasis who participate in two phase III studies (PHOENIX 1 and PHOENIX 2). Patients were randomly assigned to receive ustekinumab 45 mg or 90 mg (n = 1312; 11,624 Psoriasis Area and Severity Index [PASI] scores) or placebo (n = 665; 3278 PASI scores). Disease severity was assessed using PASI scores. A population mechanism-based exposure-response model of ustekinumab using NONMEM was developed using serum ustekinumab concentrations and PASI scores. The pharmacodynamic response effect was the reduction in PASI score. The placebo effect, although minor, was also integrated into the model. None of the covariate factors evaluated (eg, demographics, baseline disease characteristics, comorbidities) significantly contributed to the between-subject variability in the pharmacodynamic parameters. The developed exposure-response model can serve as a basis to support future alternative dosing regimens for ustekinumab in patients with moderate to severe plaque psoriasis. A robust exposure-response relationship has been confirmed for ustekinumab in psoriasis | ||
| 650 | 4 | |a Clinical Trial, Phase III | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 650 | 7 | |a Interleukin-23 |2 NLM | |
| 650 | 7 | |a Keratolytic Agents |2 NLM | |
| 650 | 7 | |a Interleukin-12 |2 NLM | |
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| 700 | 1 | |a Hu, Chuanpu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Yaowei |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Liao, Sam |e verfasserin |4 aut | |
| 700 | 1 | |a Yeilding, Newman |e verfasserin |4 aut | |
| 700 | 1 | |a Davis, Hugh M |e verfasserin |4 aut | |
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