Model-Informed Precision Dosing for Personalized Ustekinumab Treatment in Plaque Psoriasis
Background/Objectives: Implementing model-informed precision dosing (MIPD) strategies guided by population pharmacokinetic/pharmacodynamic (PK/PD) models could enhance the management of inflammatory diseases such as psoriasis. However, the extent of individual experimental data gathered during MIPD...
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| Main Authors: | , , , , , , , , |
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| Format: | Book |
| Published: |
MDPI AG,
2024-10-01T00:00:00Z.
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| Online Access: | Connect to this object online. |
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| Summary: | Background/Objectives: Implementing model-informed precision dosing (MIPD) strategies guided by population pharmacokinetic/pharmacodynamic (PK/PD) models could enhance the management of inflammatory diseases such as psoriasis. However, the extent of individual experimental data gathered during MIPD significantly influences the uncertainty in estimating individual PK/PD parameters, affecting clinical dose selection decisions. Methods: This study proposes a methodology to individualize ustekinumab (UTK) dosing strategies for 23 Spanish patients with moderate to severe chronic plaque psoriasis., considering the uncertainty of individual parameters within a population PK/PD model. Results: An indirect response model from previous research was used to describe the PK/PD relationship between UTK serum concentrations and the Psoriasis Area and Severity Index (PASI) score. A maximum inhibition drug effect (I<sub>max</sub>) model was selected, and a first-order remission constant rate of psoriatic skin lesion (k<sub>out</sub> = 0.016 d<sup>−1</sup>) was estimated. Conclusions: The MIPD approach predicted that 35% and 26% of the patients would need an optimized and intensified dosage regimen, respectively, compared to the regimen typically used in clinical practice. This analysis demonstrated its utility as a tool for selecting personalized UTK dosing regimens in clinical practice in order to optimize the probability of achieving targeted clinical outcomes in patients with psoriasis. |
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| Item Description: | 10.3390/pharmaceutics16101295 1999-4923 |