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

Area of Science:

• Pharmacology
• Dermatology
• Biostatistics

Background:

• Model-informed precision dosing (MIPD) strategies, utilizing population pharmacokinetic/pharmacodynamic (PK/PD) models, offer potential for improved management of inflammatory diseases like psoriasis.
• Uncertainty in individual PK/PD parameter estimation, influenced by experimental data, impacts clinical dose selection in MIPD.

Purpose of the Study:

• To develop and evaluate a methodology for individualizing ustekinumab (UTK) dosing strategies in Spanish patients with moderate to severe chronic plaque psoriasis.
• To incorporate parameter uncertainty within a population PK/PD model for personalized dosing decisions.

Main Methods:

• Utilized an indirect response model to link UTK serum concentrations with Psoriasis Area and Severity Index (PASI) scores.
• Employed a maximum inhibition drug effect (Imax) model and estimated a first-order remission rate constant (kout = 0.016 d⁻¹).
• Applied MIPD methodology to a cohort of 23 Spanish psoriasis patients, considering parameter uncertainty.

Main Results:

• The MIPD approach predicted that 35% of patients would benefit from an optimized UTK dosage regimen.
• An intensified dosage regimen was predicted to be necessary for 26% of patients compared to standard clinical practice.
• The PK/PD model successfully described the relationship between UTK levels and psoriasis severity.

Conclusions:

• MIPD is a valuable tool for personalized ustekinumab (UTK) dosing in psoriasis management.
• This approach can optimize the probability of achieving targeted clinical outcomes by tailoring dosage regimens.
• Individualized dosing strategies are crucial for enhancing treatment efficacy in patients with psoriasis.