Model-Informed Precision Dosing for Personalized Ustekinumab Treatment in Plaque Psoriasis
Karine Rodríguez-Fernández,
Javier Zarzoso-Foj,
Marina Saez-Bello,
Almudena Mateu-Puchades,
Antonio Martorell-Calatayud,
Matilde Merino-Sanjuan,
Elena Gras-Colomer,
Monica Climente-Martí,
Victor Mangas-Sanjuan
Affiliations
Karine Rodríguez-Fernández
Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, Spain
Javier Zarzoso-Foj
Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, Spain
Marina Saez-Bello
Pharmacy Service, Doctor Peset University Hospital, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, Spain
Almudena Mateu-Puchades
Dermatology Service, Doctor Peset University Hospital, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, Spain
Antonio Martorell-Calatayud
Dermatology Service, Hospital Manises of Valencia, 46940 Valencia, Spain
Matilde Merino-Sanjuan
Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, Spain
Elena Gras-Colomer
Pharmacy Service, Hospital Manises of Valencia, 46940 Valencia, Spain
Monica Climente-Martí
Pharmacy Service, Doctor Peset University Hospital, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, Spain
Victor Mangas-Sanjuan
Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, Spain
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 (Imax) model was selected, and a first-order remission constant rate of psoriatic skin lesion (kout = 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.