The Oxylipin Response as a New PrEdictive Biomarker of Patient Responsiveness to Biotherapy in Rheumatoid Arthritis (OPERA)

Sponsor

University Hospital, Clermont-Ferrand (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05552105

Collaborator

Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (Other), University of Southampton (Other)

Enrollment

Location

Arm

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

OPERA aims to better understand and predict the responsiveness of rheumatoid arthrits (RA) patients to biological disease modifying anti-rheumatic drugs (bDMARDs).

Our objectives will be (i) to determine, at baseline, the differences of oxylipin response between responders vs non-responders to Anti-Tumor necrosis factor (Anti TNF) and (ii) to investigate the relationships between the oxylipin response, the polyunsatured fatty acid (PUFA) content of immune cells and the cytokine response.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Other: Blood test	N/A

Detailed Description

30 RA patients starting an anti-TNF will be recruited.

Before and after 6-months of anti-TNF treatment, blood will be collected using the TruCulture system (2x 1ml in non-stimulated and Lipopolysaccharide (LPS)-stimulated TruCulture tubes) to measure Whole Blood Oxylipin Response (WBOR), cytokine response, PUFA cell content and gene expression under homeostatic and stimulated conditions (i.e. LPS).

At baseline and after 6 months of treatment, the rheumatologist will perform a clinical evaluation of their RA patients using Disease Activity Score using 28 joint-count (DAS28-CRP). Non-responders will be defined as RA patients failing to achieve good or moderate EULAR response after 6 month of anti-TNF treatment, discontinued the drug, initiated a new bDMARD, or increased dosage of oral corticosteroids greater than 10 mg/d at the second visit.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Screening

Official Title:

The Oxylipin Response as a New PrEdictive Biomarker of Patient Responsiveness to Biotherapy in Rheumatoid Arthritis.

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Apr 1, 2025

Anticipated Study Completion Date :

Apr 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Other: Cohort	Other: Blood test Before and after 6-months of anti TNF treatment, blood will be collected using the TruCulture system (2x 1ml in non-stimulated and LPS-stimulated TruCulture tubes) to measure Whole Blood Oxylipin Response, cytokine response, PUFA cell content and gene expression under homeostatic and stimulated conditions (i.e. LPS)

Arm

Intervention/Treatment

Other: Cohort

Other: Blood test

Before and after 6-months of anti TNF treatment, blood will be collected using the TruCulture system (2x 1ml in non-stimulated and LPS-stimulated TruCulture tubes) to measure Whole Blood Oxylipin Response, cytokine response, PUFA cell content and gene expression under homeostatic and stimulated conditions (i.e. LPS)

Outcome Measures

Primary Outcome Measures

Quantification of total oxylipins [Baseline]
Quantitative profiling procedure for oxylipins

Secondary Outcome Measures

Quantification of polyunsatured fatty acids in blood cells [Baseline]
Quantitative profiling procedure for polyunsatured fatty acids in blood cells (leukocytes, red blood cells and platelets)
Quantification of cytokines [Baseline]
Large panel of 21 cytokines characteristic of the inflammatory response and lymphocyte polarization. (IL-1β, IFN-α2, IFN-γ, TNF-α, MCP-1 (CCL2), IL-6, IL-8 (CXCL8), IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33, IL-5, IL-13, IL-2, IL-9, IL-10, IL-17F, IL-4, IL-22)
EULAR Response [6 month]
Non-responders will be defined as rheumatoid arthritis patients failing to achieve good or moderate EULAR response after 6 month of biological disease modifying anti rheumatic drug (bDMARD), discontinued the drug, initiated a new bDMARD, or increased dosage of oral corticosteroids greater than 10 mg/d at the second visit. EULAR response is determined by the decrease in Disease activity score (DAS) between Baseline and 6 months
Quantification of total oxylipins [6 month]
Quantitative profiling procedure for oxylipins
Quantification of cytokines [6 month]
Quantification of polyunsatured fatty acids in blood cells [6 month]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Rheumatoid patient according to ACR-EULAR (American college of rheumatology-European League Against Rheumatism) 2010 criteria,
Active disease defined by a DAS28-CRP>3.2,
Biological and targeted synthetic DMARDs naïve,
Indication for treatment with anti-TNF
Stable corticosteroid therapy ≤ 10 mg/day

Exclusion Criteria:

Contra-indications to a biological DMARDS (current or recent cancer, active infection),
Non-steroidal anti-inflammatory drugs (NSAIDs) treatment during the last 2 weeks before inclusion