Clinical trial NCT07021495: SKIN Disease Profiling by an Exploratory, pRospective, Biomarker Study in dermatoloGY Practice (SKINERGY)
Official title: A Prospective, Multi-Center, Observational Biomarker Real-World Evidence Study for In-Depth Profiling of Patients With Chronic Immune-Mediated Inflammatory Skin Diseases in Daily Practice
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Chronic Spontaneous Urticaria (CSU)
Hidradenitis Suppurativa (HS)
Psoriasis (PsO)
Atopic Dermatitis (AD)
CTCL/ Mycosis Fungoides
Keywords: Urticaria
Hives
Mast cells
Autoimmune
Autoallergic
Wheals
Angioedema
Abscess
Nodules
Sweat glands
Acne inversa
Eczema
Itchy, dry skin
Mycosis Fungoides
Skin patches
Tumors
T-cells
Lupus
Skin rash
Photosensitivity
Plaques
Scaling
Erythema
Induration
Inflammatory skin diseases
Immune-mediated
Deep phenotyping
Multi-omics
Transcriptomics
Lipidomics
Metabolomics
Proteomics
Genomics
Microbiomics
Imaging mass cytometry (CyTOF)
Real-world practice
Standard care
NextGenerationImmunoDermatology
NGID
Biomarkers
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: Erasmus Medical Center
name: Radboud University Medical Center
name: Amsterdam University Medical Center
name: UMC Utrecht
name: Maastricht University Medical Center
name: University Medical Center Groningen
name: Centre for Human Drug Research, Netherlands
First posted: 2025-06-15
Enrollment: 840
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with six different inflammatory skin diseases (AD, PSO, CLE, HS, CSU, and MF) will be enrolled. Each indication will include multiple treatment groups, with up to 40 patients per group. In total, approximately 120 patients per disease will be studied, except for PSO (4 treatment groups, N=160) and HS (2 treatment groups, N=80), covering a range of disease severities. Patients will be recruited from the local hospital where they receive standard care and will also attend study visits at this location.

Healthy volunteers will be recruited through the Centre for Human Drug Research.

Brief summary: The goal of this observational study is to comprehensively profile six immune-mediated inflammatory diseases, including atopic dermatitis (AD), plaque psoriasis (PSO), hidradenitis suppurativa (HS), cutaneous T-cell lymphoma subtype mycosis fungoides (MF), chronic spontaneous urticaria (CSU), and cutaneous lupus erythematosus (CLE) in daily practice. Data will be compared with data from healthy volunteers. This study is part of the larger NGID (Next Generation ImmunoDermatology) initiative, of which the main objective is to develop infrastructure that enables personalised patient care. The main questions the SKINERGY study aims to answer are:

* Which biomarkers can discriminate between responders and non-responders to treatment in patients with AD, CLE, CSU, HS, MF, and PSO?
* How do disease-related biomarkers in patients with AD, CLE, CSU, HS, MF, and PSO differ from those in healthy volunteers?
* Which (multi-omics) biomarkers are associated with disease subtypes and predict response or non-response to (targeted) therapies in daily clinical practice?
* How do biomarker profiles compare across different cohorts of patients with immune-mediated inflammatory skin diseases (AD, CLE, CSU, HS, MF, PSO)
* How do biomarker levels change over time in response to treatment in these patient populations?
* Which skin tissue biomarkers are associated with disease progression or treatment response?
* How do the genomic profiles of patients differ across diseases or correlate with treatment outcomes?
* Can additional imaging biomarkers enhance the characterization of disease profiles or treatment monitoring over time?

Researchers will compare both differences beween patients within a disease group in different treatment arms, as well as patients within the same treatment arm. Additionally, biomarker profiles of patients with different diseases will be evaluated. These comparisons will be made to see if shared or distinct biomarker patterns exist across diseases and treatments, which could inform patient stratification, optimize therapeutic decision-making, and identify potential targets for future interventions.

Participants will start medication according to national guidelines for the treatment of their inflammatory skin disease (AD: Cyclosporin A, anti-IL4/13, or anti-JAK; PSO: anti-TNF, anti-IL23, ani-IL17, anti-TYK2; HS: anti-TNF, anti-IL17; MF: CHLORM, TSC, PUVA-UV-B; CSU: anti-IgE, Cyclosporin A, anti-BTK\*; CLE: TSC, HCQ, MTX)

\*once approved and reimbursed in the Netherlands

Participants will:

* Take the prescribed medication for their skin disease (in line with standard care in the Netherlands).
* Visit the clinic for a study visit combined with their standard care appointment 3 times (baseline, month 3, and month 6. An additional 4th visit at month 12 is optional).
* Fill in an online set of questionnaires from home, 3 times during the study period (an additional 4th time is optional).
* Patients with CSU fill in the UAS7 (and if applicable the AAS7) daily for the study period.

Detailed description: Atopic dermatitis (AD), cutaneous lupus erythematosus (CLE), chronic spontaneous urticaria (CSU), hidradenitis suppurativa (HS), cutaneous T-cell lymphoma (CTCL, subtype mycosis fungoides, MF), and plaque psoriasis (PSO) are diverse immune-mediated inflammatory skin diseases with complex and often poorly understood pathophysiologies. Genetic, immunological, and environmental factors contribute variably across these conditions, leading to heterogeneous clinical presentations. Despite advances, the identification and validation of specific biomarkers remain limited, hampering precise diagnosis, disease subtyping, and treatment response prediction. For example, AD involves epidermal barrier defects and immune dysregulation; CLE features autoimmune mechanisms and diverse clinical subtypes; CSU results from mast cell activation; HS is driven by follicular occlusion and chronic inflammation; CTCL involves malignant T-cell proliferation in the skin; and PSO is characterized by immune-driven keratinocyte hyperproliferation. The Next Generation ImmunoDermatology project aims to address these challenges by deeply profiling these diseases to discover biomarkers that define disease endotypes and predict therapy response, ultimately enabling personalized treatment strategies.

The investigations will profile various aspects of the disease, including patient-reported outcomes, the clinician-reported outcomes, biophysical, imaging, cellular, microbiological, molecular, blood-based and tissue biomarkers.

This multicenter, open-label, longitudinal biomarker study follows 720 patients with six inflammatory skin diseases-AD, PSO, HS, CSU, CLE, and MF-for one year after starting standard-of-care treatment. Multimodal data are collected at baseline, 3, 6, and 12 months. An additional 120 healthy controls are included for baseline comparison and followed for 6 weeks. Each disease includes multiple treatment arms (N=40 per arm):

* AD: cyclosporine A; anti-IL-4/13 (dupilumab, tralokinumab, lebrikizumab); JAK1 inhibitors (upadacitinib, abrocitinib)
* PSO: anti-IL-23 (guselkumab, risankizumab, tildrakizumab); anti-IL-17 (secukinumab, ixekizumab, brodalumab, bimekizumab); anti-TNFα (adalimumab, certolizumab); TYK2 inhibitor (deucravacitinib)
* HS: anti-TNFα (adalimumab); anti-IL-17 (secukinumab, bimekizumab\*)
* MF: topical chlormethine; topical corticosteroids; phototherapy (PUVA/UV-B)
* CSU: anti-IgE (omalizumab\*); cyclosporine A; BTK inhibitors\* (remibrutinib, rilzabrutinib)
* CLE: topical corticosteroids; hydroxychloroquine; methotrexate

Eligibility criteria: Inclusion Criteria:

Patients:

1. Able to understand and provide a written informed consent prior to any study procedures
2. Male or non-pregnant female, ≥18 years of age
3. Patient is willing to refrain from extensively washing (including bathing, swimming) the target lesional skin 12 hours before every study visit day.
4. Patient is willing and able to comply with the study protocol
5. Female participants are willing to not get pregnant between M0 until M12, from study entry to the last study visit
6. The patient is willing to start the prescribed treatment.

Disease-specific inclusion criteria

For patients with AD:

To be eligible to participate in this study, a subject must meet all of the following criteria:

6. Diagnosis and history of chronic, moderate-to-severe AD (by the Eichenfield revised criteria of Hanifin and Rajka for at least 3 years before baseline visit.

7. Documented recent history (last 6 months) of eligibility for (local or systemic) treatment with immunosuppressants, biologics or JAK-inhibitors.

8. When applicable, documented recent history (last 6 months) of inadequate response to treatment with topical therapy, immunosuppressants, biologics or JAK-inhibitors.

9. Current treatment can include moisturizers, topical treatment and/or systemic treatments with preferable wash-out (see exclusion criterion #9). On-study treatment is at physician and patient discretion but must include eligibility to starting new systemic treatment.

10. EASI≥7 (moderate-to-severe disease) 11. At least one suitable target lesion at the discretion of the investigator 12. Intention to start treatment with cyclosporine A, dupilumab, tralokinumab, lebrikizumab or a JAK1-inhibitor (abrocitinib or upadacitinib)

For patients with CLE:

Participants must have a diagnosis of CLE, including SCLE, CDLE or LET that fulfil the following:

6. Confirmed CLE diagnosis by clinicopathological correlation. 7. An overall CLE Disease Area and Severity Index Activity (CLASI-A) Score ≥3 without counting any diffuse alopecia or oral ulcers.

8. Intention to start treatment with TCS, hydroxychloroquine or methotrexate (combination or mono-treatment).

If participating in the exploratory study with the skin biopsy: location of the lesion(s) selected for biopsy preferably outside the facial area (possible are e.g., neck, chest, back, limbs, scalp, ear etc.).

For patients with CSU:

6. Diagnosis of CSU (moderate to severe according to international guidelines (Zuberbier et al, 2022)) for ≥3 months and symptomatic disease despite treatment with second generation H1 antihistamines (up to fourfold the approved dose).

7.Patients currently on an antihistamine (up to fourfold the approved dose) must be on a stable dose for at least 2 weeks prior to day 1 and must maintain the same stable dose throughout the treatment period.

8. Intention to start (add-on to antihistamine) treatment of omalizumab, cyclosporine A or BTK inhibitor\*. (\*when approved and reimbursed in NL)

For patients with HS:

6. Patient with a history of signs and symptoms consistent with moderate-to-severe HS, based on IHS4 score (Zouboulis et al., 2017), for at least 1 year prior to baseline 7. Current treatment can include topical treatment. On-study treatment is at physician and patient discretion but must include eligibility to starting systemic treatment 8. Intention to start treatment with anti-TNF or anti-IL17 (secukinumab, bimekizumab\*) \*when approved and reimbursed in NL.

For patients with MF:

6. A confirmed diagnosis of CTCL MF type and stage classification via histology or clinicopathological correlation 7. For the stage IA-IIA CTCL patients: at least one patch and/or one plaque lesion is present 8. Intention to start treatment with topical chlormethine, topical corticosteroids or phototherapy (PUVA / UV-B).

For patients with PSO:

6. Diagnosed with chronic plaque psoriasis at least 6 months prior to study participation 7. PASI≥5 with at least one suitable target lesion at the discretion of the investigator 8. Current treatment can include moisturizers, topical treatment and/or systemic treatments with preferable wash-out. On-study treatment is at physician and patient discretion but must include eligibility to starting new systemic treatment 9. Intention to start treatment with biologics: anti-TNF, anti-IL23, anti-IL17 or anti-TYK2

Healthy volunteers:

All healthy volunteers must meet all of the following inclusion criteria:

1. Signed informed consent before any study-mandated procedure.
2. Male or non-pregnant female volunteers, ≥18 years of age
3. Subject is in stable good health as per judgement of the investigator based upon the results of medical history and assessments performed at baseline.
4. No clinically significant skin disease as judged by the investigator.
5. No history of hypertrophic scarring or keloid.
6. Subject is willing to refrain from extensively washing (including bathing, swimming) the skin 12 hours before every study visit.
7. Subject is willing and able to wash out and withhold any topical treatment (prescription and over-the-counter products) in the investigational area for 2 weeks prior to Day 1.
8. Subject is willing to refrain from application of any topical product (e.g. ointments, cream, or washing lotions) on the skin 24 hours prior to every study visit day.
9. Subject is willing and able to wash out any antibiotic therapy for 14 days prior to Day 1.
10. Subject is willing and able to comply with the study protocol.
11. Female participants are willing to not get pregnant from study entry to the last study visit

Exclusion Criteria:

Patients:

1. Have any other relevant skin infection/disease in the treatment area other than the investigated skin disease.
2. Subjects who have received treatment with any non-marketed drug substance (that is, an agent which has not yet been made available for clinical use following registration) within 4 weeks prior to the baseline visit.
3. Any other condition, disease, or known factor that could interfere with the study conduct or the study objectives as per judgement of the investigator. 4. Having received treatments for the investigated skin disease within the following intervals prior to the start of the study is not a strict exclusion criterion since this is a real-world study. However, preferred intervals for washout are as follows:

   * 1 week for topical treatment, e.g. corticosteroids, retinoids, vitamin D analogs, calcineurin inhibitors
   * 4 weeks for phototherapy, e.g. UVB, PUVA, PDT
   * 4 weeks for non-biologic systemic treatment, e.g. retinoids, methotrexate, cyclosporine, JAK inhibitors
   * 8 weeks for radiotherapy or surgery in the treatment area
   * 8 weeks for biologics
   * 3 months for any systemic chemotherapeutical treatment

Disease specific exclusion criteria for patients with CLE:

5. Diagnosed with SLE

Disease specific exclusion criteria for patients with CSU:

5. Treatment with omalizumab within 8 weeks prior to Day 1 6. Urticarial or angioedema symptoms such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary, acquired angioedema or drug-induced (e.g., due to C1 esterase inhibitor deficiency, ACE-inhibitor induced).

Disease specific exclusion criteria for patients with MF:

5. Ongoing uncontrolled active skin infection, other than secondary impetiginized CTCL lesions as judged by the investigator

Disease specific exclusion criteria for patients with PSO:

5. Having primarily erythrodermic, pustular or guttate psoriasis; 6. Having drug-induced psoriasis;

Healthy volunteers:

All healthy volunteers must meet none of the following exclusion criteria:

1. History of immunological abnormality (e.g. immune suppression, severe allergy, or anaphylaxis) that may interfere with study objectives as per judgement of the investigator.
2. History or symptoms of any uncontrolled, significant disease including (but not limited to), a neurological, psychiatric, endocrine, cardiovascular, respiratory, gastrointestinal, hepatic, or renal disorder that may interfere with the study objectives as per judgement of the investigator.
3. The use of systemic antibiotic therapy for \>2 months in the past 12 months.
4. The use of any immunosuppressive or immunomodulatory therapy within the past 30 days prior to Day 1.

6. Loss or donation of blood over 500mL within three months prior to baseline. Participation in an investigational drug study within 3 months prior to baseline visit or more than 4 times a year.

7. History of alcohol consumption exceeding 5 standard drinks per day on average within 3 months prior to baseline. Alcohol consumption will be prohibited for at least 24 hours preceding each study visit.

8. Positive urine test for drugs or history of abuse at baseline. 9. Exposure to high doses of UV radiation is not permitted within 3 weeks of the first study visit until the end of the study 10. Extreme physical activities are not permitted within 48 hours before each study visit 11. Any other condition, disease, or known factor that could interfere with the study conduct or the study objectives as per judgement of the investigator.

Primary outcomes:
measure: Lipidomics of the stratum corneum and OLINK
timeFrame: Baseline - month 12
measure: Cutaneous microbiome
timeFrame: Baseline - month 12
measure: Serum biomarkers
timeFrame: Baseline - month 12
measure: Plasma biomarkers
timeFrame: Baseline - month 12
measure: Eczema Area and Severity Index (EASI)
timeFrame: Baseline - month 12
measure: objective Severity Scoring of Atopic Dermatitis (oSCORAD)
timeFrame: Baseline - month 12
measure: Validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA-AD)
timeFrame: Baseline - month 12
measure: Cutaneous LE Disease Area and Severity Index Activity (CLASI-A)
timeFrame: Baseline - month 12
measure: Total Sum Score
timeFrame: Baseline - month 12
measure: The Cutaneous Lupus Activity-Investigator Global Assessment (CLA-IGA)
timeFrame: Baseline - month 12
measure: International Hidradenitis Suppurativa Severity Score System (IHS4)
timeFrame: Baseline - month 12
measure: Modified Severity-Weighted Assessment Tool (mSWAT)
timeFrame: Baseline - month 12
measure: Cutaneous Lymphoma Activity and Severity Index (CAILS)
timeFrame: Baseline - month 12
measure: Psoriasis Area and Severity Index (PASI)
timeFrame: Baseline - month 12
measure: Physician Global Assessment (PGA)
timeFrame: Baseline - month 12
measure: Body Surface Area (BSA)
timeFrame: Baseline - month 12
measure: Psoriasis Area and Severity Index - High Discrimination (PASI-HD)
timeFrame: Baseline - month 12
Secondary outcomes:
measure: User experience and subjective burden questionnaire
timeFrame: Baseline, month 6
measure: Patient reported outcomes
timeFrame: Baseline - month 12
measure: Skin barrier function by Electrical Impedance Spectroscopy (EIS)
timeFrame: Baseline - month 12
measure: Line-Field Confocal Optical Coherence Tomography (LC-OCT)
timeFrame: Baseline - month 12
measure: Laser Speckle Contrast Imaging (LSCI)
timeFrame: Baseline - month 12
measure: 3D Multispectral imaging
timeFrame: Baseline - month 12
measure: Colorimetry
timeFrame: Baseline - month 12
measure: Skin punch biopsies
timeFrame: Baseline, month 3
measure: Patient genotyping
timeFrame: Baseline
measure: Activity Tracking Sleep
timeFrame: Baseline - month 6
measure: Activity Tracking Steps
timeFrame: Baseline - month 6
measure: Activity Tracking Heartrate
timeFrame: Baseline - month 6
measure: Blood sampling for RNAsequencing
timeFrame: Baseline, month 3
measure: Dermatology Life Quality Index (DLQI)
timeFrame: Baseline - month 12
measure: Treatment Satisfaction Questionnaire for Medication (TSQM)
timeFrame: Month 3 - month 12
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: Baseline - month 12
measure: Numerical Rating Scale (NRS) for Pruritus and Burning Sensation/Pain
timeFrame: Baseline - month 12
measure: 5-D Itch Scale
timeFrame: Baseline - month 12
measure: Chronic Skin Disease on Daily Life (ISDL)
timeFrame: Baseline - month 12
measure: Itch Severity and Burden Questionnaire (ISBQ)
timeFrame: Baseline - month 12
measure: Penn State Worry Questionnaire (PSWQ)
timeFrame: Baseline - month 12
measure: Impact of Chronic Skin Disease on Daily Life (ISDL)
timeFrame: Baseline - month 12
measure: Expectancies and and avoidance behaviour (G-EEE)
timeFrame: Baseline - month 12
measure: Social Sensory Processing Questionnaire - Short Form (SPSQ-S)
timeFrame: Baseline - month 12
measure: Type D Personality Scale (DS-14)
timeFrame: Baseline - month 12
measure: Perceived Stress Scale (PSS)
timeFrame: Baseline - month 12
measure: P-Scale Short
timeFrame: Baseline - month 12
measure: Self-Efficacy for Managing Chronic Disease (SEMCD) scale
timeFrame: Baseline - month 12
measure: Recap of Atopic Eczema (RECAP)
timeFrame: Baseline - month 12
measure: Patient-Oriented Eczema Measure (POEM)
timeFrame: Baseline - month 12
measure: Angioedema Activity Score over 7 days (AAS7)
timeFrame: Baseline - month 12
measure: Urticaria Activity Score over 7 days (UAS7)
timeFrame: Baseline - month 12
measure: Urticaria Control Test (UCT)
timeFrame: Baseline - month 12
measure: Hidradenitis Suppurativa Quality of Life (HiSQoL)
timeFrame: Baseline - month 12
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
state: Gelderland
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center+
state: Limburg
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Center
state: North-Holland
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
state: South-Holland
city: Leiden
country: Netherlands
facility: Centre for Human Drug Research
state: South-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
state: South-Holland
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
Study officials:
References: