Approximately, 40 to 50% of patients with rheumatoid arthritis (RA), the most frequent inflammatory arthritide, are non responders to the consensual 1st line of treatment : methotrexate. In these patients, it is well demonstrated that the addition of other immunomodulatory drug(s) often results in a significant improvement. However, the best option regarding the drug(s) to add remains unclear. Rheumatologists are currently used to adding a targeted therapy, such as anti-TNFα, and more recently abatacept or tocilizumab. Triple therapy using 3 conventional disease-modifying drugs (DMARDs), methotrexate or leflunomide+salazopyrine+hydroxychloroquine could be an alternative option to targeted therapies, all the more as they have a more favorable safety profile and a much lower cost. Uncertainty remains regarding the superiority of targeted therapies on triple therapy in methotrexate or leflunomide insufficient responders (IR). Investigators decided to address this issue by performing a randomized controlled pragmatic trial.

Inclusion Criteria:

• Patient with rheumatoid arthritis according to EULAR/ACR 2010 criteria
• DAS28-CRP>3.2
• Insufficient response to methotrexate at a weekly dose≥15mg after at least 3 months or to leflunomide at a dose of 10 (in case 20 mg are not well tolerated) to 20 mg per day after 3 months of treatment
• RA radiographic erosions and/or serum rheumatoid factor associated to anti-Cyclic Citrullinated Peptide (Anti-CCP)
• Age greater or equal to 18 years
• Written informed consent, dated and signed before initiating any trial-related procedure
• Affiliation to a social insurance system
• Women of child bearing potential, negative β-HCG assay (Human chorionic gonadotropin)
• Effective method of birth control during the study and continuing after the discontinuation of the investigational drug or study. The duration will depend on the drug used (referred to the summary product characteristic).

Exclusion Criteria:

• Previous treatment with or contraindication to targeted therapies (biologic or JAK/STAT inhibitor)
• Previous treatment with triple therapy
• Other inflammatory arthritis except RA associated with Sjögren's syndrome
• Contraindication to all biologics/ JAK/STAT inhibitors or to methotrexate, leflunomide, sulfasalazine and hydroxychloroquine
• Corticosteroids at a dose >15 mg/d of equivalent prednisone for at least 4 weeks before the inclusion
• Absence of tuberculosis screening
• Patient who cannot be followed during 12 months
• Pregnancy, breastfeeding, desire of pregnancy in the 12 months
• Drug addiction, addiction to alcohol
• Participation in a clinical study with an investigational product within 4 weeks prior to the start of the study treatment
• Women of child bearing potential, unless they are using an effective method of birth control
• Patient under law protection
• Prisoners