Personalized Secukinumab Treatment in Patients with Plaque Psoriasis Using Model-Informed Precision Dosing

Area of Science:

• Pharmacometrics
• Pharmacokinetics/Pharmacodynamics (PK/PD)
• Dermatology

Background:

• Model-informed precision dosing (MIPD) enhances patient care for inflammatory disorders like psoriasis.
• Population PK/PD models are crucial for MIPD strategies.
• Uncertainty in individual PK/PD parameters, influenced by clinical data, impacts dose selection.

Purpose of the Study:

• To propose a personalized dosing strategy for secukinumab (SCK) in plaque psoriasis patients.
• To incorporate uncertainty of individual PK/PD parameters within a population model.
• To optimize SCK dosage regimens for moderate-to-severe plaque psoriasis.

Main Methods:

• Developed a population PK/PD model for 22 Spanish plaque psoriasis patients.
• Utilized an indirect response model to link SCK concentrations with Psoriasis Area and Severity Index (PASI) scores.
• Applied a maximum inhibition (Imax) model within a turnover mechanism to describe PASI score changes.

Main Results:

• Established the relationship between SCK serum concentrations and PASI scores.
• Estimated a first-order remission rate constant (kout = 0.11 day⁻¹) for psoriatic lesions.
• The model explained PASI score variations during secukinumab treatment.

Conclusions:

• MIPD strategy suggests 50% of patients may need optimized SCK regimens.
• 14% of patients might benefit from intensified SCK dosage compared to current standards.
• This approach serves as a valuable tool for individualized SCK dosing in chronic plaque psoriasis, enhancing treatment response probability.