National Cohort of Subjects at Risk of Developing Rheumatoid Arthritis

This is a multicenter interventional cohort study. The goal of this cohort is to analyze the factors associated with the risk of developing clinical arthritis, considering individual or combined exposures, in patients at high risk of rheumatoid arthritis (RA).

Four groups of adults will be included:

* Group 1: 50 subjects at very high risk of RA: ACPA≥2 N or (ACPA\>N and rheumatoid factor≥2 N) + presence of clinically suspicious arthralgia (CSA criteria ≥4) * Group 2: 50 subjects at high risk of RA: ACPA≥2 N or (ACPA\>N and rheumatoid factor≥2 N) without clinically suspicious arthralgia (CSA criteria \<4) * Group 3: 25 asymptomatic subjects, 1st degree relatives of subjects with RA (negative controls) * Group 4: 25 patients with early RA prior to any disease-modifying therapy (positive controls) Patients in the control groups will be included based on the same age and sex as patients in the risk groups (1 \& 2) in the recruiting center.

The primary endpoint is the occurrence of clinical arthritis, confirmed by ultrasound, after two years of follow-up in the at-risk RA groups (Groups 1 \& 2).

This may be explained by the following exposures or their combinations: smoking, occupational exposure, physical activity, diet, hormonal exposure, drug exposure, trauma and psychological stress...

Other factors that may contribute to the occurrence of clinical arthritis include:

* Clinical elements and questionnaires assessing the other symptoms of the individuals (PRO) (subjective clinical suspicion of arthralgia CSA, painful joints at inclusion, BMI, stool consistency, functional respiratory signs, etc.) * Comorbidities and antecedents via CNAM pathology mapping and drug exposure via data on dispensing in towns from the SNDS * Current biology: ACPA levels, rheumatoid factor levels and isotypes, CRP levels at baseline, etc. * Ultrasound and MRI abnormalities.

The controls groups (groups 3\&4) will allow for a cross-sectional analysis, comparing at-risk RA subjects with healthy individuals who share the same genetic background. They will have a single visit at baseline without follow-up.

However, the at-risk RA groups (groups 1 \& 2) will have four visits (M0, M6, M12 et M24). In addition to routine care examinations performed in RA risk situations, subjects will undergo blood and stool sample collection at baseline and at one year.

All subjects regardless of group, will undergo the following baseline assessments: MRI of the dominant hand or painful hand, a lactulose absorption test (to assess intestinal permeability), hair and saliva collection, a Schirmer test, and, in some centers, an induced sputum test (to assess pulmonary mucosa). Ultrasound of the hands and feet, as well as specific questionnaires assessing the exposome, will be conducted at all visits.

• Quantitative difference in Food Frequency Questionnaire (FFQ) between the 4 groups of subjects included, varying from never or rarely to daily or multiple times per day. [Срок оценки: At baseline]
• Quantitative difference in National Observatory for Physical Activity and Sedentariness -Physical Activity Questionnaire (ONAPS-PAQ) expressed in MET (Metabolic Equivalent of Task) per week between the 4 groups of subjects included. [Срок оценки: At baseline]
• Quantitative difference in patient-reported exposure outcome Alcohol and Substance Involvement Screening Test (ASSIST) score between the 4 groups of subjects included. [Срок оценки: At baseline]
• Quantitative difference in Fagerström Test for Nicotine Dependence (FTND) score between the 4 groups of subjects included. [Срок оценки: At baseline]
• Compare the exposure to pollution between the 4 groups of subjects included. "Exposure to pollution will be assessed by cross-referencing residential addresses with the Chimère database. [Срок оценки: At baseline]
• Qualitative difference in a self-report integrated questionnaire for diagnosis of all functional gastrointestinal disorders in adults between the 4 groups of subjects included. [Срок оценки: At baseline]
• Quantitative difference in patient-reported Francis score for Irritable Bowel Syndrome (IBS) between the 4 groups of subjects included. [Срок оценки: At baseline]
• Qualitative difference in patient-reported clinical outcome of Sleep Apnea (Berlin questionnaire) between the 4 groups of subjects included. [Срок оценки: At baseline]
• Quantitative difference in Visual Analog Scale (VAS) score for patient's pain between the 4 groups of subjects included. [Срок оценки: At baseline]
• Quantitative difference in Visual Analog Scale (VAS) score for patient's fatigue between the 4 groups of subjects included. [Срок оценки: At baseline]
• Quantitative difference in Visual Analog Scale (VAS) score for patient's disease activity between the 4 groups of subjects included. [Срок оценки: At baseline]
• Quantitative difference in Visual Analog Scale (VAS) score for disease activity on the opinion of the physician between the 4 groups of subjects included. [Срок оценки: At baseline]