To address this hypothesis we carried out a biopsy-driven, randomized clinical trial in RA (R4RA)9 in which TNF-inhibitor-inadequate responders were randomized to either rituximab (anti-CD20 monoclonal antibody) or tocilizumab (anti-IL6R monoclonal antibody) after stratification according to synovial B cell signatures. The gene discussed is TNF; the disease is rheumatoid arthritis.