Drug insight: different mechanisms of action of tumor necrosis factor antagonists-passive-aggressive behavior?

Nat Clin Pract Rheumatol. 2007 Apr;3(4):227-33. doi: 10.1038/ncprheum0438.


Antagonists of tumor necrosis factor (TNF) have revolutionized the treatment of selected inflammatory diseases. In rheumatology, this has been most notable for ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis. Despite their specificity for TNF, these agents, which include the soluble p75 receptor etanercept and the anti-TNF antibodies adalimumab and infliximab, have demonstrated differential clinical efficacy in studies of rheumatoid arthritis; patients who do not respond to one antagonist often respond to another. Therapeutic disparity of these agents is also seen in specific diseases, most notably Crohn's disease. Differences in pharmacodynamics, pharmacokinetics and mechanisms of action, as well as disease heterogeneity, have been proposed to account for these effects. Reverse signaling by transmembrane TNF in response to anti-TNF antibodies, but not soluble receptor, might also influence the therapeutic response.

Publication types

  • Review

MeSH terms

  • Adalimumab
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents / pharmacology*
  • Antirheumatic Agents / therapeutic use
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Etanercept
  • Humans
  • Immunoglobulin G / pharmacology*
  • Immunoglobulin G / therapeutic use
  • Infliximab
  • Receptors, Tumor Necrosis Factor / drug effects
  • Receptors, Tumor Necrosis Factor / physiology
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Rheumatic Diseases / drug therapy
  • Rheumatic Diseases / pathology
  • Signal Transduction / physiology
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / physiology


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab
  • Etanercept