Therapeutic Drug Monitoring of Secukinumab in Psoriasis Patients.

Study Overview
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Brief Summary
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Biologics such as secukinumab are currently the most effective treatment option for patients with moderate to severe psoriasis. But they are costly for healthcare systems and still described according to a'one dose fits all' dosing regimen, leading to potential over-and undertreatment. In this study we aim to investigate the predictive value of early serum trough levels of secukinumab and determine the therapeutic window of secukinumab in psoriasis patients.

Detailed Description
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Patients will be included after signing informed consent. After inclusion, patients will continue on standard dosing schedule of secukinumab (i.e. subcutaneous injections once a week for 5 weeks (300 mg) followed by subcutaneous injections every 4 weeks). During each study visit blood will be taken in order to quantify Ctroughs and/or anti-drug antibodies towards secukinumab. In addition, Psoriasis Area and Severity Index (PASI) and Investigator's Global Assessment (IGA) score will be evaluated by a physician. Patients complete the Dermatology Life Quality Index (DLQI) and European quality of life EQ-5D instrument at each visit.

Official Title
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Evaluation of the Predictive Value of Early Serum Trough Concentrations and Anti-drug Antibodies of Secukinumab and the Development of a Concentration Response Curve of Secukinumab for Psoriasis Patients.

Conditions
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Psoriasis Vulgaris

Intervention / Treatment
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* Procedure: Venapuncture
* Other: Patient questionnaires


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have a clinical or histological diagnosis of chronic plaque-type psoriasis Participants must sign an ICF indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study Exclusion Criteria: Participants who have currently a predominant nonplaque form of psoriasis Participants who are pregnant, nursing or planning a pregnancy Participants who are unable or unwilling to undergo multiple venapunctures Participants who are treated according to a different dosing schedule than standard dosing of secukinumab

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: A prospective, open label, non-randomized study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard of care - secukinumab<br>Patients will continue to receive secukinumab according to the standard dosing schedule: subcutaneous injections once a week for 5 weeks, then every 4 weeks (300 mg). | Procedure: Venapuncture<br>* Blood samples will be collected to determine the serum trough levels and anti-drug antibodies of secukinumab.<br>Other: Patient questionnaires<br>* The study participants will complete the Dermatology Quality of Life (DLQI) and EQ-5D-5L questionnaire at each study visit.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Predictive value of early serum trough concentrations of secukinumab | Prediction of the clinical response (PASI) at week 12 and/or week 24 based on serum trough concentrations of secukinumab measurements taken from week 0,1,2,3 and/or 4. | Week 0 until week 24 of treatment | 
| Predictive value of early anti-drug antibodies of secukinumab | Prediction of the clinical response (PASI) at week 12 and/or week 24 based on anti-drug antibodies (ADA) measurements taken from week 0,1,2,3 and/or 4. | Week 0 until week 24 of treatment | 
| Development of the therapeutic window of secukinumab in psoriasis | Defining a therapeutic window for secukinumab based on serum trough concentrations corresponding with adequate clinical response | Week 0 until week 52 of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLQI | The DLQI (Dermatology Life Quality Index) (range 0-30) is a dermatology specific quality of life (QoL) instrument designed to assess the impact of the disease on participant's QoL. It is a ten item questionnaire that, in addition to evaluated overall QoL, can be used to assess six different aspects that may affect QoL: 1) symptoms and feelings, 2) daily activities, 3) leasure, 4) work or school performances, 5) personal relationships, and 6) treatment. The scoring of each question is as follows: Very much - scored 3; A lot - scored 2; A little - scored 1; Not at all - scored 0; Not relevant - scored 0; Question 7, 'prevented work or studying' - scored 3. The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. | Week 0 until week 52 of treatment | 
| EQ-5D-5L | The EQ-5D-5L comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems.The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits of the five dimensions can be combined into a 5- digit number that describes the patients' health state. | Week 0 until week 52 of treatment | 
| EQ VAS | The EQ VAS (Visual Analogue Scale) (range 0-10) records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement. | Week 0 until week 52 of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Therapeutic drug monitoring, Psoriasis, Secukinumab