Therapeutic agents for patients with rheumatoid arthritis and an inadequate response to tumour necrosis factor-α antagonists

BACKGROUND: Rheumatoid arthritis (RA) is a disabling autoimmune disease; unless adequately controlled, patients have a poor long-term prognosis. Tumour necrosis factor (TNF)-alpha antagonists have provided relief for many RA patients; however, despite their efficacy, some patients do not respond or fail to maintain initial response. In the UK, patients with an inadequate response to TNF-alpha antagonists have limited options, as the National Institute of Clinical Excellence (NICE) currently only recommend switching to an alternative TNF-alpha antagonists if discontinuation occurs due to safety during the first 6 months of treatment. The EU has approved three biological agents, rituximab, abatacept, and tocilizumab, for patients with RA with an inadequate response to TNF-alpha antagonists. OBJECTIVE: This review examines the clinical experience with two therapies targeting key immune cells involved in RA -- rituximab (lyses B-cells), and abatacept (T-cell co-stimulation modulator) -- specifically focusing on patients with an inadequate response to TNF-alpha blockade. METHODS: Phase II/III clinical trials and original studies were identified using Medline and Pubmed; articles assessing the efficacy and/or safety of rituximab or abatacept in patients with RA refractory to TNF-alpha blockade were reviewed. CONCLUSIONS: Clinical data for rituximab and abatacept demonstrate that both reduce disease activity in TNF-alpha antagonist inadequate responders, suggesting that agents with alternative mechanisms of action, such as those targeting key immune cells, may be useful in this patient population.