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

Study Overview
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Brief Summary
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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.

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

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Other: Tapering and/or discontinuation of treatment based on AI-guidance
* Other: No tapering and/or discontinuation of treatment based on AI-guidance
* Other: Tapering and/or discontinuation of treatment based on standard of care
* Other: No tapering and/or discontinuation of treatment based on standard of care


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| RA in remission who performed synovial biopsy before treatment change<br> | Other: Tapering and/or discontinuation of treatment based on standard of care<br>* After synovial tissue biopsy, pharmacological treatment (cDMARDs or bDMARDs) are tapered first and then bDMARDs and/or cDMARDs are discontinued based on standard of care<br>Other: No tapering and/or discontinuation of treatment based on standard of care<br>* Ongoing therapeutic are not changed (tapered or discontinued) after synovial biopsy performance based on standard of care<br>|
| RA in remission eligible to synovial biopsy before treatment change<br> | Other: Tapering and/or discontinuation of treatment based on AI-guidance<br>* After synovial tissue biopsy, pharmacological treatment (cDMARDs or bDMARDs) are tapered first and then bDMARDs and/or cDMARDs are discontinued based on AI-guidance<br>Other: No tapering and/or discontinuation of treatment based on AI-guidance<br>* Ongoing therapeutic are not changed (tapered or discontinued) after synovial biopsy performance based on AI-guidance<br>Other: Tapering and/or discontinuation of treatment based on standard of care<br>* After synovial tissue biopsy, pharmacological treatment (cDMARDs or bDMARDs) are tapered first and then bDMARDs and/or cDMARDs are discontinued based on standard of care<br>Other: No tapering and/or discontinuation of treatment based on standard of care<br>* Ongoing therapeutic are not changed (tapered or discontinued) after synovial biopsy performance based on standard of care<br>|
| Subjects asymptomatic for joint inflammation without ACPA/RF positivity<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establishment of cellular and molecular atlas of remission RA | 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. | months 1-12 | 

Secondary Outcome Measures

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