Dissecting the Cellular and Molecular Atlas of Rheumatoid Arthritis in Sustained Remission to Identify Pathways Maintaining Remission and Triggering Flares

Recruiting

• Conditions: Rheumatoid Arthritis
• Interventions: Other: Tapering and/or discontinuation of treatment based on standard of care; Other: Tapering and/or discontinuation of treatment based on AI-guidance; Other: No tapering and/or discontinuation of treatment based on AI-guidance; Other: No tapering and/or discontinuation of treatment based on standard of care

• Registration Number: NCT05952440
• Lead Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Brief Summary

The FLARE-RA study will have the following research objectives:

A) To establish the cellular and molecular atlas of remission RA achieved with different therapeutics aimed to identify (i) cell clusters/pathways driving disease flare or maintaining remission and (ii) provide an evidence base for developing ML tools for predicting flares.

B) To test the performance of a ML-derived algorithm on longitudinal remission RA cohort in a biopsy-driven study.

C) To dissect the cellular and molecular mechanisms of remission maintenance and joint flares.

Detailed Description

Not available

Study Timeline

• Status Verified: 2023-05
• Study Start: 2023-07-11
• Study First Submitted: 2023-07-11
• Study First Submitted QC: 2023-07-11
• Study First Posted: 2023-07-19
• Last Update Submitted: 2023-07-20
• Last Update Posted: 2023-07-21
• Primary Completion: 2026-05-10
• Study Completion: 2026-05-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 130

Inclusion Criteria

• Rheumatoid Arthritis classified based on the 2010 EULAR/ACR Classification Criteria
• Stable treatment with cDMARDs and/or bDMARDs (≥12 months)
• Stable remission status (at least DAS28-CRP<2.6) (≥6 months)
• No concomitant steroid treatment (≥6 months)
• Absence of Power-Doppler signal at ultrasound assessment (wrist, MCP, PIP, Knee, ankle and II-V MTP bilaterally) in 3 evaluations 3 months apart.

Exclusion Criteria

• DAS28-CRP≥2.6
• Presence of Power-Doppler signal ≥1 at ultrasound assessment (wrist, MCP, PIP, Knee, ankle and II-V MTP bilaterally)
• Other chronic inflammatory disease

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
RA in remission who performed synovial biopsy before treatment change	Tapering and/or discontinuation of treatment based on standard of care	-
RA in remission eligible to synovial biopsy before treatment change	No tapering and/or discontinuation of treatment based on AI-guidance	-
RA in remission eligible to synovial biopsy before treatment change	Tapering and/or discontinuation of treatment based on AI-guidance	-
RA in remission eligible to synovial biopsy before treatment change	Tapering and/or discontinuation of treatment based on standard of care	-
RA in remission eligible to synovial biopsy before treatment change	No tapering and/or discontinuation of treatment based on standard of care	-
RA in remission who performed synovial biopsy before treatment change	No tapering and/or discontinuation of treatment based on standard of care	-

Primary Outcome Measures

Name	Time	Method
Establishment of cellular and molecular atlas of remission RA	months 1-12	To establish the cellular and molecular atlas of remission RA achieved with different therapeutics aimed to identify (i) cell clusters/pathways driving disease flare or maintaining remission and (ii) provide an evidence base for developing ML tools for predicting flares.

Secondary Outcome Measures

Name	Time	Method
To test the performance of a ML-derived algorithm on longitudinal remission RA cohort in a biopsy-driven study.	months 13-36	To test the performance of a ML-derived algorithm on longitudinal remission RA cohort in a biopsy-driven study.
To dissect the cellular and molecular mechanisms of remission maintenance and joint flares	months 13-36	To dissect the cellular and molecular mechanisms of remission maintenance and joint flares in in vivo and in vitro systems

Trial Locations

Locations (4)

Newcastle University; 🇬🇧 Newcastle Upon Tyne, United Kingdom

Research into Inflammatory Arthritis Centre Versus Arthritis (RACE); 🇬🇧 Glasgow, United Kingdom

Hospital Clinic and Fundació Clinic per la Recerca Biomèdica; 🇪🇸 Barcelona, Spain

Division of Rheumatology; 🇮🇹 Rome, Italy