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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Other: Blood test


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cohort<br> | Other: Blood test<br>* 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)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantification of total oxylipins | Quantitative profiling procedure for oxylipins | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantification of polyunsatured fatty acids in blood cells | Quantitative profiling procedure for polyunsatured fatty acids in blood cells (leukocytes, red blood cells and platelets) | Baseline | 
| Quantification of cytokines | 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) | Baseline | 
| EULAR Response | 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 | 6 month | 
| Quantification of total oxylipins | Quantitative profiling procedure for oxylipins | 6 month | 
| Quantification of cytokines |  | 6 month | 
| Quantification of polyunsatured fatty acids in blood cells |  | 6 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anti TNF, Oxylipin, Cytokine, Polyunsatured fatty acid