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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Other: Blood test

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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France
    • Chu Clermont-Ferrand
    • Principal Investigator: Anne TOURNADRE

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Collaborators: University of Southampton; Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2022
• Primary Completion (Anticipated): April 1, 2025
• Study Completion (Anticipated): April 1, 2025

Study Registration Dates

• First Submitted: September 16, 2022
• First Submitted That Met QC Criteria: September 20, 2022
• First Posted (Actual): September 23, 2022

Study Record Updates

• Last Update Posted (Actual): September 23, 2022
• Last Update Submitted That Met QC Criteria: September 20, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Cytokine; Anti TNF; Oxylipin; Polyunsatured fatty acid
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: RBHP 2022 TOURNADRE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No