Personalized Secukinumab Treatment in Patients with Plaque Psoriasis Using Model-Informed Precision Dosing
<b>Background/Objectives:</b> Patient care and control of inflammatory disorders, such as psoriasis, can be improved by model-informed precision dosing (MIPD) techniques based on population pharmacokinetic/pharmacodynamic (PK/PD) models. Clinical dose selection decisions based on MIPD st...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/16/12/1576 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846103199488933888 |
|---|---|
| author | Karine Rodriguez-Fernandez Javier Zarzoso-Foj Marina Saez-Bello Almudena Mateu-Puchades Antonio Martorell-Calatayud Matilde Merino-Sanjuan Elena Gras-Colomer Monica Climente-Marti Victor Mangas-Sanjuan |
| author_facet | Karine Rodriguez-Fernandez Javier Zarzoso-Foj Marina Saez-Bello Almudena Mateu-Puchades Antonio Martorell-Calatayud Matilde Merino-Sanjuan Elena Gras-Colomer Monica Climente-Marti Victor Mangas-Sanjuan |
| author_sort | Karine Rodriguez-Fernandez |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> Patient care and control of inflammatory disorders, such as psoriasis, can be improved by model-informed precision dosing (MIPD) techniques based on population pharmacokinetic/pharmacodynamic (PK/PD) models. Clinical dose selection decisions based on MIPD strategies need to take account of the uncertainty associated with the individual PK/PD model parameters, which is determined by the quantity of individual observational data collected in clinical practice. <b>Methods:</b> The aim of this study was to propose an approach for personalized dosage regimens of secukinumab (SCK) in 22 Spanish patients with plaque psoriasis, whose severity level was considered moderate to severe, taking into account the uncertainty associated with individual parameters in a population-based PK/PD model. <b>Results:</b> The link between SCK serum concentrations and Psoriasis Area and Severity Index (PASI) scores was explained using an indirect response model. A maximum inhibition (I<sub>max</sub>) drug effect model was applied to limit the progression of psoriatic skin lesions within the turnover PD mechanism, which explains the changes in PASI scores during treatment. A first-order remission rate constant for psoriatic lesions (k<sub>out</sub> = 0.11 day<sup>−1</sup>) was estimated. <b>Conclusions:</b> According to the MIPD strategy, 50% of patients would require an optimized regimen and 14% would require an intensified dosage regimen in comparison to current clinical treatment. This research has shown its usefulness as a tool for choosing individualized SCK dosage regimens in patients with long-lasting plaque psoriasis to improve the probability of achieving satisfactory response levels. |
| format | Article |
| id | doaj-art-eeab755094af43f5862687133b9033dc |
| institution | Kabale University |
| issn | 1999-4923 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj-art-eeab755094af43f5862687133b9033dc2024-12-27T14:46:33ZengMDPI AGPharmaceutics1999-49232024-12-011612157610.3390/pharmaceutics16121576Personalized Secukinumab Treatment in Patients with Plaque Psoriasis Using Model-Informed Precision DosingKarine Rodriguez-Fernandez0Javier Zarzoso-Foj1Marina Saez-Bello2Almudena Mateu-Puchades3Antonio Martorell-Calatayud4Matilde Merino-Sanjuan5Elena Gras-Colomer6Monica Climente-Marti7Victor Mangas-Sanjuan8Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, SpainDepartment of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, SpainPharmacy Service, Doctor Peset University Hospital, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, SpainDermatology Service, Doctor Peset University Hospital, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, SpainDermatology Service, Hospital Manises of Valencia, 46940 Manises, SpainDepartment of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, SpainPharmacy Service, Hospital Manises of Valencia, 46940 Manises, SpainPharmacy Service, Doctor Peset University Hospital, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, SpainDepartment of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, Spain<b>Background/Objectives:</b> Patient care and control of inflammatory disorders, such as psoriasis, can be improved by model-informed precision dosing (MIPD) techniques based on population pharmacokinetic/pharmacodynamic (PK/PD) models. Clinical dose selection decisions based on MIPD strategies need to take account of the uncertainty associated with the individual PK/PD model parameters, which is determined by the quantity of individual observational data collected in clinical practice. <b>Methods:</b> The aim of this study was to propose an approach for personalized dosage regimens of secukinumab (SCK) in 22 Spanish patients with plaque psoriasis, whose severity level was considered moderate to severe, taking into account the uncertainty associated with individual parameters in a population-based PK/PD model. <b>Results:</b> The link between SCK serum concentrations and Psoriasis Area and Severity Index (PASI) scores was explained using an indirect response model. A maximum inhibition (I<sub>max</sub>) drug effect model was applied to limit the progression of psoriatic skin lesions within the turnover PD mechanism, which explains the changes in PASI scores during treatment. A first-order remission rate constant for psoriatic lesions (k<sub>out</sub> = 0.11 day<sup>−1</sup>) was estimated. <b>Conclusions:</b> According to the MIPD strategy, 50% of patients would require an optimized regimen and 14% would require an intensified dosage regimen in comparison to current clinical treatment. This research has shown its usefulness as a tool for choosing individualized SCK dosage regimens in patients with long-lasting plaque psoriasis to improve the probability of achieving satisfactory response levels.https://www.mdpi.com/1999-4923/16/12/1576psoriasissecukinumabpharmacokinetic/pharmacodynamic |
| spellingShingle | Karine Rodriguez-Fernandez Javier Zarzoso-Foj Marina Saez-Bello Almudena Mateu-Puchades Antonio Martorell-Calatayud Matilde Merino-Sanjuan Elena Gras-Colomer Monica Climente-Marti Victor Mangas-Sanjuan Personalized Secukinumab Treatment in Patients with Plaque Psoriasis Using Model-Informed Precision Dosing Pharmaceutics psoriasis secukinumab pharmacokinetic/pharmacodynamic |
| title | Personalized Secukinumab Treatment in Patients with Plaque Psoriasis Using Model-Informed Precision Dosing |
| title_full | Personalized Secukinumab Treatment in Patients with Plaque Psoriasis Using Model-Informed Precision Dosing |
| title_fullStr | Personalized Secukinumab Treatment in Patients with Plaque Psoriasis Using Model-Informed Precision Dosing |
| title_full_unstemmed | Personalized Secukinumab Treatment in Patients with Plaque Psoriasis Using Model-Informed Precision Dosing |
| title_short | Personalized Secukinumab Treatment in Patients with Plaque Psoriasis Using Model-Informed Precision Dosing |
| title_sort | personalized secukinumab treatment in patients with plaque psoriasis using model informed precision dosing |
| topic | psoriasis secukinumab pharmacokinetic/pharmacodynamic |
| url | https://www.mdpi.com/1999-4923/16/12/1576 |
| work_keys_str_mv | AT karinerodriguezfernandez personalizedsecukinumabtreatmentinpatientswithplaquepsoriasisusingmodelinformedprecisiondosing AT javierzarzosofoj personalizedsecukinumabtreatmentinpatientswithplaquepsoriasisusingmodelinformedprecisiondosing AT marinasaezbello personalizedsecukinumabtreatmentinpatientswithplaquepsoriasisusingmodelinformedprecisiondosing AT almudenamateupuchades personalizedsecukinumabtreatmentinpatientswithplaquepsoriasisusingmodelinformedprecisiondosing AT antoniomartorellcalatayud personalizedsecukinumabtreatmentinpatientswithplaquepsoriasisusingmodelinformedprecisiondosing AT matildemerinosanjuan personalizedsecukinumabtreatmentinpatientswithplaquepsoriasisusingmodelinformedprecisiondosing AT elenagrascolomer personalizedsecukinumabtreatmentinpatientswithplaquepsoriasisusingmodelinformedprecisiondosing AT monicaclimentemarti personalizedsecukinumabtreatmentinpatientswithplaquepsoriasisusingmodelinformedprecisiondosing AT victormangassanjuan personalizedsecukinumabtreatmentinpatientswithplaquepsoriasisusingmodelinformedprecisiondosing |