Exploration of the Cellular and Molecular Mechanisms in Patients Receiving Biotherapies Targeting the IL-23/IL-17 Axis in Cutaneous Psoriasis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Profiling of open chromatin regions
研究概览
简要总结
This is a research study involving humans, of the interventional type with minimal risks and constraints (RIPH2). It is a monocentric, non randomized prospective study aiming to better understand the mechanisms of the response to anti-IL-23 biologics in psoriasis patients attending the dermatology department of hospital Cochin (APHP).
详细描述
The aim of this project is to study the cellular and molecular mechanisms in patients receiving anti-IL-23 biologics as treatment for cutaneous psoriasis, in order to improve the understanding of the role of IL-23/IL-17 axis in this pathology.
This objective is detailed in three specific aims:
- Define the effects of IL-23 on gene expression and cytokine production in innate and adaptive T lymphocytes in patients with skin psoriasis and correlate it with the patient's genotype
- Identify at the single cell level the cells expressing IL-23R and/or producing IL-17 in the skin of patients with skin psoriasis;
- Characterize the in vivo effects of anti-IL-23 therapy on the immune responses of patients with skin psoriasis, by analysing gene expression and protein secretion in whole blood cultures before and after treatment; The secondary objective of this study is to identify mechanisms of non-response to anti-IL-23 therapy in cutaneous psoriasis patients.
The study population to be included are patients affected by cutaneous psoriasis, requiring systemic biological treatment and attended to in the Dermatology Department of the Cochin Hospital. Patients will be divided into two groups: Group 1 patients will participate once before initiation of therapy, Group 2 will participate before and after initiation of anti-IL-23 biologic treatment.
Group 1: 10 patients with cutaneous psoriasis for the phenotypic and transcriptional analyses of T cell populations in peripheral blood. These patients will be sampled once before initiation of biotherapy.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients:
- •Adults (>18 years)
- •Presenting with cutaneous psoriasis
- •Patients have signed an informed consent
- •Beneficiary of the health insurance, except for the AME Only for patients of Group 1
- •Patients require systemic treatment for psoriasis
- •Patients are naïve to biological therapies
- •Only for patients of Group 2:
- •Patients requiring treatment with anti-IL-23 biologics (guselkumab, risankizumab, tildrakizumab) upon referent physician's decision.
- •Patients are naïve to biological therapies or have received only one biologic, with a "wash-out" period of at least 4 months
- •Non inclusion Criteria:
- •Patient is minor
- •Patient is pregnant or breastfeeding
- •Patient is immunocompromised
- •Patient is under legal protection, curatorship, guardianship
- •Patient refuses consent
- •Patient is unable to comply with study requirements for geographic, social or psychiatric reason.
- •Beneficiary of the AME Only for patients of Group 1
- •Patient has received biologics Only for patients of Group 2
- •Patient has a contraindication to the chosen biotherapy
- •Patient has received biologics within the last 4 months
- •Patient has been treated with 2 or more biologics
- •Patient has already received an anti-IL-23 biologic
排除标准
- 未提供
结局指标
主要结局
Profiling of open chromatin regions
时间窗: 7 years
Profiling of open chromatin regions (ATAC seq), of the transcriptome (RNA-seq), of the genome (genotyping), and of cytokine expression (Luminex technology) in T lymphocytes from patients with cutaneous psoriasis, untreated or treated with IL-23 in vitro
Single cell transcriptome analysis
时间窗: 7 years
Single cell transcriptome analysis of skin biopsies from patients with cutaneous psoriasis, before and after anti-IL-23 therapy.
Analysis of the frequencies of MAIT, iNKT, γδ TCR+, CD4+ et CD8+ T cells
时间窗: 7 years
Analysis of the frequencies of MAIT, iNKT, γδ TCR+, CD4+ et CD8+ T cells in the peripheral blood of patients with cutaneous psoriasis, before and after initiation of anti-IL-23 treatment to analyse the effect of anti-IL-23 therapy on the immune responses.
次要结局
- Definition of an immune response signature(7 years)
- Identification of epigenetic modifications in cell populations in the skin and/or in circulating immune cells by anti-IL-23 therapy(7 years)