title: Therapeutic agents for patients with rheumatoid arthritis and an inadequate response to tumour necrosis factor-alpha antagonists.
abstract: 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.
authors.affiliation: Institute for Cellular Medicine (Muscoskeletal Research Group), Newcastle University, 4th Floor, Catherine Cookson Building, Framlington Place, Newcastle upon Tyne, UK. j.d.isaacs@ncl.ac.uk
authors.forename: John D
authors.initials: JD
authors.lastname: Isaacs
mesh_terms: D000069594:Abatacept; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D019317:Evidence-Based Medicine; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069283:Rituximab; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D018796:Immunoconjugates; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab; D000069594:Abatacept