Synovial Tissue and Blood Signature of Rheumatoid Arthritis Patients With Disease Flare After Treatment Discontinuation for Sustained Remission.

Synovial Tissue and Blood Signature to Personalize the Management of Rheumatoid Arthritis Patients With Disease Flare After Biological DMARDs Discontinuation for Sustained Remission.

Flares of immune-mediated inflammatory diseases, as Rheumatoid Arthritis (RA), are a major burden for patients in routine care. They occur unpredictably, adding to the physical and psychological burden of the condition. In this study we will deeply dissect the synovial tissue and peripheral blood signature of RA in sustained remission eligible to treatment discontinuation to better understand the individualized factors determining disease flare once biological treatment is discontinued. We expect that the combined study of synovial tissue, imaging and peripheral blood derived biomarkers, associated with disease flare after treatment discontinuation in RA in remission, will provide a tool for the routine assessment of RA eligible to treatment discontinuation reducing the relapse rate and increasing the optimization of the use of expensive pharmacological treatments only for patients still needing them.

Study Overview

• Status: Active, not recruiting
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Procedure: Evaluation of subclinical inflammation

• Study Type: Observational
• Enrollment (Actual): 200

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00168
    • Division of Rheumatology
  • Lombardia
    • Brescia, Lombardia, Italy, 25121
      • Centro di Ricerca E. Menni - Fondazione Poliambulanza Brescia
  • Puglia
    • Bari, Puglia, Italy, 70100
      • UOC Reumatologia - Policlinico di Bari

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with Rheumatoid Arthritis in stable remission (DAS<1.6 for at least 6 months) and under treatment with stable dose of conventional, synthetic or biological DMARDs. All patients at the time of enrolment must fulfil the ultrasound criteria of Power Doppler negativity of knee, wrist, II-V MCP and II-V MTP bilaterally and any other reported painful joint not included in the screening ultrasound protocol.

Description

Inclusion Criteria:

• Diagnosis of RA following the 2010 ACR/EULAR classification criteria
• Age ≥18 and ≤75 years
• Sustained remission (DAS<1.6 for at least 3 sequential evaluations 6months apart).
• Without evidence of ultrasound detected synovitis (Power Doppler negative in knee, wrist, II-V MCP, II-V PIP and II-V MTP bilaterally).
• Patients under treatment with stable dose of conventional, synthetic or biological DMARDs.
• Patients without steroid treatment in the last 6 months.

Exclusion Criteria:

• With other diagnosis of chronic joint diseases rather than RA.
• Unable to participate to the clinical outpatient follow-up.
• Exposed to steroid treatment within 6 months from study screening.
• With evidence of ultrasound detected synovitis (Power Doppler positivity) in other joints than the ones included in the screening visit.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
RA patients in sustained clinical and ultrasound remission not changing treatment	Procedure: Evaluation of subclinical inflammation; Minimally invasive synovial tissue biopsy for the semiquantitative and qualitative assessment of synovial immune and stromal cells; Peripheral blood collection for MBDA assessment and phenotyping of immune cells;
RA patients in sustained clinical and ultrasound remission changing treatment	Procedure: Evaluation of subclinical inflammation; Minimally invasive synovial tissue biopsy for the semiquantitative and qualitative assessment of synovial immune and stromal cells; Peripheral blood collection for MBDA assessment and phenotyping of immune cells;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease flare rate	24 months

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2019
• Primary Completion (Actual): March 14, 2022
• Study Completion (Anticipated): March 14, 2023

Study Registration Dates

• First Submitted: March 2, 2023
• First Submitted That Met QC Criteria: March 2, 2023
• First Posted (Actual): March 14, 2023

Study Record Updates

• Last Update Posted (Actual): March 14, 2023
• Last Update Submitted That Met QC Criteria: March 2, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: peripheral blood; disease flare; synovial tissue; sustained remission
• 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: 2667

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