The Role of IL-23 in Chronic Inflammatory Disease: Exploring the Cellular and Molecular Targets of IL-23 Signaling in Peripheral and Axial Spondyloarthritis (SpA23)

This is a research study involving humans, of the interventional type with minimal risks and constraints (RIPH2). It is a multicentric, non randomized prospective study aiming to better understand the mechanisms of the response to anti-IL-23 biologics in Spondyloarthritis patients attending the rheumatology department of Cochin, Saint-Antoine, Henri-Mondor hospitals (APHP) and Maison-Blanche Hospital (Reims).

Study Overview

• Status: Recruiting
• Conditions: Spondyloarthritis
• Intervention / Treatment: Other: Blood sampling; Other: synovial aspiration

Detailed Description

The aim of this project is to improve our understanding of the role of IL-23 in the pathophysiology of axial SpA and peripheral SpA.

This objective is detailed in three specific aims:

1. Define the effects of IL-23 on gene expression and cytokine production in innate and adaptive T lymphocytes from patients with SpA, and correlate them with the patient's genotype;
2. Phenotypically characterize immune cell populations in peripheral blood and in synovial fluid from peripheral SpA patients and identify at the single cell level the cells expressing the IL-23 receptor and/or producing IL-17.

The study population to be included are patients affected by SpA, attended to in the Rheumatology Departments of Cochin Hospital, Saint-Antoine Hospital Henri-Mondor hospitals in Paris (APHP) and Maison-Blanche Hospital in Reims. Participants will be divided into two groups: Group 1 comprises patients diagnosed with axial SpA, Group 2 SpA patients with peripheral SpA or psoriatic arthritis.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lars ROGGE, Dr; Phone Number: +33140613822; Email: lars.rogge@pasteur.fr

Study Locations

• France
  • Créteil, France, 94000
    • Not yet recruiting
    • Hôpital Henri-Mondor, AP-HP - Service de Rhumatologie
    • Contact: Pascal CLAUDEPIERRE, Pr; Phone Number: +33149814704; Email: pascal.claudepierre@aphp.fr
    • Contact: Pascal CLAUDEPIERRE, Pr
  • Paris, France
    • Recruiting
    • Hôpital Cochin, AP-HP - Department of Dermatology B
    • Contact: Corinne MICELI-RICHARD, Pr; Phone Number: +33 6 1292 9487; Email: corinne.miceli@aphp.fr
    • Contact: Corinne MICELI-RICHARD, Pr
  • Paris, France
    • Recruiting
    • Hôpital Saint-Antoine, AP-HP - Service de Rhumatologie
    • Contact: Francis BERENBAUM, Pr; Phone Number: + 33 1 4928 2520; Email: francis.berenbaum@aphp.fr
    • Contact: Francis BERENBAUM, Pr
    • Contact: Jérémie SELLAM, Dr
  • Reims, France, 51092
    • Not yet recruiting
    • Hôpital Maison Blanche - Service de Rhumatologie
    • Contact: Jean-Hugues SALMON, Pr; Phone Number: 33 3 26 78 43 73; Email: jhsalmon@chu-reims.fr
    • Contact: Jean-Hugues SALMON, Pr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age : Adults (>18 years)
• Satisfying ASAS diagnostic criteria for SpA
• Patient has active disease, defined by the presence of active synovitis, tendinitis, or dactylitis or significant inflammatory pain of the spine, judged by the examining clinician to be due to SpA.
• Informed consent signed
• Beneficiary of health insurance, except for the AME

Only for patients of Group 1 • Patient is naïve to biological therapies

Only for patients of Group 2

• Patient is affected by peripheral SpA (ASAS criteria) or psoriatic arthritis, with inflammation of peripheral joints
• Patient requires aspiration, as part of standard care

Non inclusion criteria:

• Patient is minor
• Patient is pregnant or breastfeeding
• Patient is immunocompromised
• Patient has received biological therapy with 2 or more biologics
• Patient is receiving corticosteroid treatment > 10 mg per day
• Patient is under legal protection, curators, guardianship
• Patient refuses consent
• Previous history of alcoholism, drug addiction, psychological problems, severe concomitant conditions that could invalidate the patient's consent or limit the patient's compliance to the treatment protocol.
• Beneficiary of the AME

Only for group 1

• Patient has received biological therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with axial spondyloarthritis participating in the study; People with axial spondylarthritis (60 participants),	Other: Blood sampling; A 51 mL blood sample will be collected during the study
Experimental: Patients with peripheral spondyloarthritis participating in the study; People with peripheral spondylarthritis or psoriatic arthritis (30 participants).	Other: Blood sampling; A 51 mL blood sample will be collected during the study; Other: synovial aspiration; If synovial aspiration is required in standard care for patients with peripheral spondylarthritis. Medical waste product will be collected for the study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Profiling of open chromatin regions	Profiling of open chromatin regions (ATAC seq) in T lymphocytes, cultured in the presence or absence of IL-23in order to define the effects of IL-23 on gene expression and cytokine production in innate and adaptive T lymphocytes from patients with SpA, and correlate them with the patient's genotype	4 years
Profiling of transcriptome	Profiling of the transcriptome (RNA-seq) in T lymphocytes, cultured in the presence or absence of IL-23in order to define the effects of IL-23 on gene expression and cytokine production in innate and adaptive T lymphocytes from patients with SpA, and correlate them with the patient's genotype	4 years
Profiling of the genome	Profiling of the genome (genotyping) in T lymphocytes, cultured in the presence or absence of IL-23in order to define the effects of IL-23 on gene expression and cytokine production in innate and adaptive T lymphocytes from patients with SpA, and correlate them with the patient's genotype	4 years
Profiling of cytokine expression	Profiling of cytokine expression (Proximity Extension Assay technology) in T lymphocytes, cultured in the presence or absence of IL-23 in order to define the effects of IL-23 on gene expression and cytokine production in innate and adaptive T lymphocytes from patients with SpA, and correlate them with the patient's genotype	4 years
Single cell transcriptome analysis	Single cell transcriptome analysis of cells from patients with peripheral SpA will be performed to characterize immune cell populations in peripheral blood and in synovial fluid and identify at the single cell level the cells expressing the IL-23 receptor and/or producing IL-17;	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure lymphocyte levels to explore the effects of anti-IL23 treatment on the immune responses of axSpA patients	Define the effects in vitro of IL-23 blockade on immune responses in the peripheral blood of axSpA patients, using whole blood culture assays to profile stimulated protein secretion and gene expression, in the presence or absence of IL-23 inhibitors. As this therapy is not employed for the treatment of axSpA, we will characterize the in vitro effects of anti-IL-23 blockade on the immune responses of patients with axSpA, by analysing gene expression and protein secretion in whole blood cultures in the presence or absence of anti-IL-23 treatment. We will isolate MAIT, γδ TCR+, CD4+CCR6+ and CD8+CCR6+ (enriched in IL-23R+) T cell populations from peripheral blood of psoriasis patients and stimulate them through the T cell receptor (TCR), in the presence or absence of IL-23.	4 years

Collaborators and Investigators

• Sponsor: Institut Pasteur
• Collaborators: Janssen Biotech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2022
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: February 25, 2022
• First Submitted That Met QC Criteria: March 11, 2022
• First Posted (Actual): March 22, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 21, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Spondyloarthritis; immune response; interleukin-23; anti-IL-23 therapy
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases; Infections; Bone Diseases, Infectious; Spinal Diseases; Spondylarthropathies; Ankylosis; Axial Spondyloarthritis; Spondylitis; Spondylarthritis
• Other Study ID Numbers: 2021-087; 2021-A02801-40 (Other Identifier: ANSM)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No