Molecular Signatures in Inflammatory Skin Disease

Study Overview
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Brief Summary
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This pilot project intends to examine the utility of a systems medicine approach to identify regulatory networks and their perturbation in psoriasis and atopic dermatitis, and to obtain a comprehensive perspective on disease and disease control by integrating and modelling data across multiple cellular levels and time following specific blockade of single pathophysiological factors through use of licensed biologics during routine care as systems biology challenge. To this end, ultra-deep phenotyping and prospective molecular characterization in short time-intervals and different disease equilibrium states will be carried out in targeted small sets of patients. The different layers and types of clinical and molecular information will then be integrated (integrative personal omics profiling iPOP) for generating insights into disease pathways and for extraction of molecular signatures that correspond to clinical severity scores. It will provide a good starting point for planning future trials aimed at identifying biological patterns useful for guiding targeted treatment.

Detailed Description
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This is an exploratory study with the aim to identify molecular profiles and signatures in skin and blood that correlate with inflammatory skin disease, disease activity and disease progression, and that are associated with possible disease subtypes/endotypes. Primary target variables are differentially expressed genes (alone or in combination), secondary target variables are genetic, immunological and microbiological signatures. Influencing variables of interest include age of manifestation, disease duration, disease activity/severity, disease progression, comorbidities and therapy/treatment. Obtained biomaterial will be used for molecular profiling including DNA/RNA sequencing, ELISA, mass spectrometry, flow cytometry to identify markers and/or signatures that can correlate with individual disease courses.

Official Title
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Systematic Profiling of Anti-cytokine Signatures in the Treatment of Chronic Inflammatory Skin Disorders

Conditions
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Atopic Dermatitis, Psoriasis

Intervention / Treatment
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* Drug: Ustekinumab
* Drug: Infliximab
* Drug: Secukinumab
* Drug: Dupilumab
* Drug: Brodalumab
* Drug: Ixekizumab
* Drug: Baricitinib
* Drug: Abrocitinib
* Drug: Upadacitinib
* Drug: Tralokinumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to provide written informed consent and comply with the protocol Diagnosis of chronic psoriasis or atopic dermatitis PASI score ≥ 10 or EASI score ≥ 16 Investigator Global Assessment (IGA) ≥ 3 Subject receives systemic therapy within routine care (in-label use of biologics) Exclusion Criteria: Subject is unable to provide written informed consent or comply with the protocol. Having used immunosuppressive/immunomodulating therapy or phototherapy within 4 weeks before the baseline visit. Treatment of selected skin areas to be examined with topical corticosteroid or topical calcineurin inhibitor within 1 week before the baseline visit.
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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Psoriasis patients receiving ustekinumab<br>Ustekinumab | Drug: Ustekinumab<br>* Subject receives Ustekinumab open-label as per guidelines<br>|
| Psoriasis patients receiving infliximab<br>Infliximab | Drug: Infliximab<br>* Subject receives Infliximab open-label as per guidelines<br>|
| Psoriasis patients receiving secukinumab<br>Secukinumab | Drug: Secukinumab<br>* Subject receives Secukinumab open-label as per guidelines<br>|
| Atopic dermatitis patients receiving dupilumab<br>Dupilumab | Drug: Dupilumab<br>* Subject receives Dupilumab open-label as per guidelines<br>|
| Psoriasis patients receiving brodalumab<br>Brodalumab | Drug: Brodalumab<br>* Subject receives Brodalumab open-label as per guidelines<br>|
| Psoriasis patients receiving Ixekizumab<br>Ixekizumab | Drug: Ixekizumab<br>* Subject receives Ixekizumab open-label as per guidelines<br>|
| Atopic dermatitis patients receiving tralokinumab<br>Tralokinumab | Drug: Tralokinumab<br>* Subject receives Tralokinumab open-label as per guidelines<br>|
| Atopic dermatitis patients receiving baricitinib<br>Baricitinib | Drug: Baricitinib<br>* Subject receives Baricitinib open-label as per guidelines<br>|
| Atopic dermatitis patients receiving abrocitinib<br>Abrocitinib | Drug: Abrocitinib<br>* Subject receives Abrocitinib open-label as per guidelines<br>|
| Atopic dermatitis patients receiving upadacitinib<br>Upadacitinib | Drug: Upadacitinib<br>* Subject receives Upadacitinib open-label as per guidelines<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of molecular profiles over time | Changes of immune cell composition, transcriptome, proteome and microbiome signatures | Baseline and week 1, week 2, week 12, week 52 | 
| Changes of molecular profiles associated with disease severity/remission | Changes of immune cell composition, transcriptome, proteome and microbiome signatures | Baseline and week 1, week 2, week 12, week 52 | 
| Changes of molecular profiles associated with treatment | Changes of immune cell composition, transcriptome, proteome and microbiome signatures | Baseline and day 1, day 7, day 14, day 84, day 364 | 
| Changes of molecular profiles associated with treatment response | Changes of immune cell composition, transcriptome, proteome and microbiome signatures | Baseline and week 1, week 2, week 12, week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Eczema Area and Severity Index (EASI) score | Clinical severity score | Baseline and week 1, week 2, week 12, week 52 | 
| Change in Score of Atopic Dermatitis (SCORAD) | Clinical severity score | Baseline and week 1, week 2, week 12, week 52 | 
| Change in Psoriasis Area Severity Index (PASI) score | Clinical severity score | Baseline and week 1, week 2, week 12, week 52 |