Plaque psoriasis may be an ideal model disease to explore potential therapeutic effects of immunosuppressive agents, given the easy accessibility of inflammatory lesions. In this study, the applicability of a systems dermatology approach is investigated in order to better assess the efficacy of psoriasis treatments at an early clinical stage. Up to this point, the clinical manifestation and regression of psoriasis is not yet sufficiently characterized with a multimodal state-of-the-art evaluation tool. The in-house developed 'DermaToolbox' enables the determination and subsequent integration of different diseaserelated biomarkers, including clinical, biophysical, molecular, cellular, and imaging markers as well as patient reported outcomes
Psoriasis is a common skin disorder affecting up to an estimated 3% of the world's population. The most prevalent form of psoriasis, called psoriasis vulgaris or plaque psoriasis, is characterized by the presence of sharply demarcated erythematous plaques covered with white scales. These lesions can occur all over the body, but are most often seen on the extensor surface of the joints, nether regions and on the scalp. Patients can experience excessive itch, pain and sometimes bleeding of the lesions. Moreover, the visual appearance of psoriatic lesions can severely impact the patients psychological state and quality of life. An abundancy of different factors contributes to the pathogenesis of psoriasis. However, aberrant inflammatory reactions in the skin are thought to be the underlying cause. Excessive infiltration of immune cells in the skin and their interactions with cutaneous resident cells results in the hyper proliferation of keratinocytes and subsequent thickening of the epidermis. Indeed, more and more immunosuppressive biologicals targeting specific components of the immune system, like tumor necrosis factor alpha (TNFα), interleukin (IL-)17 and IL-23, have shown excellent efficacy in treating psoriasis Plaque psoriasis may be an ideal model disease to explore potential therapeutic effects of immunosuppressive agents, given the easy accessibility of inflammatory lesions and the good willingness of patients to participate in clinical studies. In this study, the applicability of a systems dermatology approach is investigated in order to better assess the efficacy of psoriasis treatments at an early clinical stage. Up to this point, the clinical manifestation and regression of psoriasis is not yet sufficiently characterized with a multimodal state-of-the-art evaluation tool. The in-house developed 'DermaToolbox' enables the determination and subsequent integration of different disease-related biomarkers, including clinical, biophysical, molecular, cellular, and imaging markers as well as patient-reported outcomes
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
37
100 mg guselkumab administered subcutaneously
Sodiumchloride 0,9% solution for injection
Centre for Human Drug Research
Leiden, Netherlands
Psoriasis Area and Severity Index (PASI) Assessment
Psoriasis Area and Severity Index (PASI) combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease).
Time frame: from day -14 to day 168
Physicians Global Assesment (PGA) Assessment
Physicians Global Assesment (PGA) is a 4-point scale ranging from 0 (no disease) to 4 (maximal disease).
Time frame: from day -14 to day 168
Percentage body surface affected (%BSA) Assessment
Percentage body surface affected (%BSA) is the area of lesional skin as a percentage of the total body surface
Time frame: from day -14 to day 168
digital PASI
Digital Psoriasis Area and Severity Index (dPASI) calculated from standardized total body photography
Time frame: from day -14 to day 168
Erythema measurement of the skin
Redness of the skin will be determined using a colorimeter
Time frame: from day -14 to day 168
Multispectral imaging
The redness and superficial morphology of (non-)lesional skin sites will be determined using a multispectral imaging system
Time frame: from day -14 to day 168
Laser Speckle Contrast imaging
The cutaneous microcirculation of (non-)lesional skin sites will be monitored over a 30 second timespan with a laser speckle contrast imager
Time frame: from day -14 to day 168
Thermography
Body surface temperature of (non-)lesional skin will be determined using a thermal imaging infrared camera
Time frame: from day -14 to day 168
Patient reported outcomes
Patients will be asked to report on their condition through an NRS scale (0 (better)- 10 (worse)) for sleeplessness, itch and quality of life. Additionally, patients image their lesions on a daily basis using a mobile device.
Time frame: from day -14 to day 168
Activity Tracking Heartrate
Subjects are requested to wear a smartwatch at all times which heart rate (beats per minute)
Time frame: from day -14 to day 168
Activity Tracking Steps
Subjects are requested to wear a smartwatch at all times which register steps (amount of steps taken)
Time frame: from day -14 to day 168
Activity Tracking Sleep
Subjects are requested to wear a smartwatch at all times which register sleep (hrs, minutes, seconds of rest)
Time frame: from day -14 to day 168
Cells/ml; Circulating immune cell subsets
Blood be drawn during using a venipuncture during visits and analyzed for the presence of immune cells (e.g. CD4+ and CD8+ T-Cells) using flow cytometry
Time frame: from day -14 to day 168
Circulating protein biomarkers
Blood be drawn during using a venipuncture during visits and analyzed for the presence of various chemokines and cytokines (e.g. CCL20, CCL17, CXCL8)
Time frame: from day -14 to day 168
Anti-drug antibodies
The occurrence of antibodies directed against guselkumab will be monitored during the treatment period (ng/ml)
Time frame: from day 0 to day 168
Blister immune cell subsets
Blisters will be induced on the non-lesional skin and the blister exudate aspirated. Blister exudate will be analyzed for the presence of immune cells (e.g. CD4+ and CD8+ T-Cells) using flow cytometry
Time frame: from day 0 to day 112
Blister protein biomarkers
Blisters will be induced on the non-lesional skin and blister fluid aspirated. Blister fluid will be analyzed for the presence of various chemokines and cytokines (e.g. CCL20, CCL17, CXCL8) (ng/ml)
Time frame: from day 0 to day 112
Immunohistochemistry of biopsies
Biopsies will be sectioned and stained for the determination of the epidermal homeostasis (proliferation, differentiation and thickness) and infiltration of cellular immune subsets (e.g. presence of CD4 and CD8).
Time frame: day 0 to day 112
Transcriptome of biopsies
Biopsies will be analyzed with an untargeted next-generation sequencing approach.
Time frame: day 0 to day 112
Cutaneous microbiome
The microbiome is collected by swabbing. The abundance of bacteria is thereafter determined using next-generation sequencing.
Time frame: from day -14 to day 112
Fecal microbiome
The bacterial composition of stool samples is determined using next-generation sequencing.
Time frame: from day 0 to day 112
Skin surface biomarkers
Superficial protein biomarkers are samples using a FibroTx Patch. Afterwards, these patches are extracted and the presence of protein biomarkers (e.g. HBD-3) determined using ELISA.
Time frame: from day -14 to day 112
Lipidomics of the stratum corneum
Tape stripping will be performed on (non-)lesional skin and lipids are subsequently extracted from the tape and analyzed using Liquid Chromatogrpahy-Mass Spectormetry. (ng/cm2)
Time frame: from day -14 to day 112
Skin barrier function
The trans epidermal water loss of (non-)lesional skin will be determined as function of the inside-out barrier function of the skin. (g/m2/h)
Time frame: from day -14 to day 168
Patient genotyping
A whole blood sample will be used to scan for common mutations in genes implicated in psoriasis using next-generation sequencing.
Time frame: day -14
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