Model-Informed Precision Dosing for Personalized Ustekinumab Treatment in Plaque Psoriasis

Pharmaceutics. 2024 Oct 4;16(10):1295. doi: 10.3390/pharmaceutics16101295.

ABSTRACT

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_max) model was selected, and a first-order remission constant rate of psoriatic skin lesion (k_out = 0.016 d^-1) 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.

PMID:39458624 | PMC:PMC11510411 | DOI:10.3390/pharmaceutics16101295