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.

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

Experimental groups will include, the following classes of patients:

1. Rheumatoid Arthritis in sustained clinical and ultrasound remission afferent to the Division of Rheumatology - Fondazione Policlinico Universitario A. Gemelli IRCCS, in Rome who already underwent synovial tissue biopsy for the routine clinical assessment of tissue inflammation (retrospective cohort) (n=40).
2. Rheumatoid Arthritis in sustained clinical and ultrasound remission afferent to the Division of Rheumatology - Fondazione Policlinico Universitario A. Gemelli IRCCS, in Rome or to the Hospital Clinic and Fundació Clinic per la Recerca Biomèdica, in Barcelona eligible to synovial tissue biopsy for the routine clinical assessment of tissue inflammation (prospective cohort) (n=40 for each center).
3. Subjects asymptomatic for joint inflammation without ACPA/RF positivity (n=10) (University of Glasgow).