TNF and rheumatoid arthritis: Because more than 50% of patients with rheumatoid arthritis show low or absent B-cell infiltration in the main disease tissue (joint synovium), the rituximab versus tocilizumab in anti-TNF inadequate responder patients with rheumatoid arthritis (R4RA) trial was designed and independently supported by the UK NIHR to determine whether target expression levels (CD20 B cells) and B-cell associated molecular signatures in the synovial tissue can provide a mechanistic explanation for drug mode of action and treatment response.