Biologic therapy for rheumatoid arthritis: clinical efficacy and predictors of response

BioDrugs. 2009;23(2):111-24. doi: 10.2165/00063030-200923020-00004.


Rheumatoid arthritis (RA) is a chronic, disabling disease of the synovial joints, thought to be autoimmune in origin. The emergence of biologic therapies has proven to be highly successful in effectively treating RA in the majority of cases. However, the cost of these agents is high and some patients do not respond to these drugs, or they suffer from adverse events. This article will review the currently available data on efficacy and the clinical, genetic, and biomarkers of response to these biologic therapies in RA. The anti-tumour necrosis factor-alpha (anti-TNFalpha) agents, adalimumab, etanercept and infliximab, act to neutralize the pro-inflammatory cytokine. Response to these agents is higher in patients receiving concurrent disease modifying anti-rheumatic drugs or non-steroidal anti-inflammatory drugs, in those with lesser disability, and in non-smokers. Many genetic predictors of response have been investigated, such as the shared epitope, the TNF gene and its receptors, but none have been absolutely confirmed. Synovial expression of TNFalpha has been suggested as a biomarker of response, while anti-cyclic citrullinated peptide antibody and rheumatoid factor (RF)-positivity predict poor response. Newer biologic agents include the interleukin (IL)-1 receptor antagonist anakinra, the B-cell depleting agent rituximab, the selective costimulation modulator abatacept, and the anti-IL-6 receptor monoclonal antibody tocilizumab. No genetic studies of response to these agents have been performed to date. However, it has been reported that low synovial infiltration of B cells and complete B-cell depletion after the first rituximab infusion are predictors of good response to this agent.

Publication types

  • Review

MeSH terms

  • Abatacept
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Biomarkers / blood
  • Humans
  • Immunoconjugates / therapeutic use
  • Immunologic Factors / therapeutic use*
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use
  • Prognosis
  • Rituximab
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents
  • Biomarkers
  • Immunoconjugates
  • Immunologic Factors
  • Interleukin 1 Receptor Antagonist Protein
  • Tumor Necrosis Factor-alpha
  • Rituximab
  • Abatacept
  • tocilizumab