The pathogenesis of rheumatoid arthritis: new insights from old clinical data?

Nat Rev Rheumatol. 2012 Mar 13;8(4):235-43. doi: 10.1038/nrrheum.2012.23.


Despite their different targets, biologic agents used for blockade of TNF and IL-6, inhibition of T-cell co-stimulation and B-cell depletion all have similar beneficial effects on the outcome of rheumatoid arthritis (RA). This observation raises questions as to whether the targets of these therapies might all be involved in a common pathogenetic pathway. However, blockade of TNF and IL-6 has a similar inhibitory effect on joint damage progression in patients with either early or late disease. In comparison, B-cell depletion and inhibition of T-cell co-stimulation seem to have a somewhat delayed effect on joint damage (compared with cytokine inhibition), which suggests that these approaches affect upstream pathogenetic events. This article discusses these disparities and presents hypotheses as to whether clinical trial data can be used to determine at which point a biologic agent might interfere with the pathogenetic cascade in RA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arthritis, Rheumatoid* / drug therapy
  • Arthritis, Rheumatoid* / etiology
  • Arthritis, Rheumatoid* / immunology
  • Biological Therapy / methods*
  • Disease Models, Animal
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / immunology
  • T-Lymphocytes / immunology*
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / immunology


  • IL6 protein, human
  • Immunosuppressive Agents
  • Interleukin-6
  • Tumor Necrosis Factor-alpha