Blockade of signalling by pro-inflammatory cytokines, such as tumour necrosis factor (TNF) and interleukin-6 (IL-6), using monoclonal antibodies has revolutionized outcomes for patients with severe rheumatoid arthritis but, in common with all currently available biologics, these drugs remain subject to a ‘therapeutic ceiling’, with true remission unattainable for the majority. This evidence concerns the gene TNF and rheumatoid arthritis.