Combination of Baricitinib and Anti-TNF in Rheumatoid Arthritis

As stated by the European League Against Rheumatism (EULAR) and the Société Française de Rhumatologie (SFR), treatment of patients with rheumatoid arthritis (RA) should target sustained remission or at least low disease activity. However, despite significant advances based on various combinations of conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and biologic DMARDs, RA therapies meet treatment goals only in some patients: * 40 to 50% of patients with early RA, treated with methotrexate (MTX) monotherapy as first-line therapy, * 20 to 30% of patients treated with a combination of MTX and biologic as second-line therapy. * Less than 10% of patients treated with a combination of MTX and another targeted DMARD, such as baricitinib, as third-line therapy. Therefore, new strategies targeted at achieving a higher percentage of remission are needed, that do not require waiting for multiple failed therapies. Combinations of biologics have shown synergistic improvement of symptoms in murine models of RA relative to the improvement observed with either agent alone. However, in RA patients, only five randomised clinical trials (RCTs) have explored the efficacy and safety of combining tumour necrosis factor (TNF) inhibitor with another biologic (anakinra, abatacept, rituximab or bimekizumab). Baricitinib is a selective, reversible and competitive inhibitor of Janus kinases (Jaki). This treatment is efficient in a number of therapeutic scenarios in RA and showed a clinical superiority over adalimumab in one RCT (RA-BEAM study in MTX inadequate responders). Of note, baricitinib inhibits many of the pro-inflammatory cytokines involved in the pathogenesis of RA but does not block signalling downstream of TNF. Owing to the interest in combining different mechanisms of action, the investigators plan to assess the efficacy and safety of combination therapy with baricitinib and a TNF inhibitor. The investigators are aware that combining targeted therapies is