In this study, we aim to address a number of critical unanswered questions taking advantage of a unique synovial tissue biomedical resource of well-characterised RA patients matched for disease stage and treatment exposure, emerging from the Pathobiology of Early Arthritis Cohort (PEAC) and the first worldwide biopsy-driven randomised clinical trial: Rituximab versus tocilizumab in anti-TNF inadequate responder (ir) patients with rheumatoid arthritis (R4RA). The gene discussed is TNF; the disease is rheumatoid arthritis.