Pharmacology of TNF blockade in rheumatoid arthritis and other chronic inflammatory diseases

Curr Opin Pharmacol. 2010 Jun;10(3):308-15. doi: 10.1016/j.coph.2010.01.005. Epub 2010 Feb 19.

Abstract

Tumor necrosis factor-alpha (TNF) has been unequivocally validated as a therapeutic target in a number of immune-mediated inflammatory disorders (IMIDs). There is now increasing choice of biologic agents within the class all of which successfully neutralize sTNF. But approaches to TNF inhibition differ and currently include mAbs (infliximab, adalimumab, and golimumab), either chimeric or human in sequence, a PEGylated Fab' fragment (certolizumab), and an IgG1-TNFR2 fusion protein (etanercept). It is emerging that the pharmacological properties of these three anti-TNF subtypes differ with respect to Fc function, binding of tmTNF and the possible consequences of this, as well as the ability to form complexes. The mode of administration of each agent, clearance and the local tissue concentrations achieved may also confer unique characteristics of relevance with respect to efficacy and safety.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / physiopathology
  • Chronic Disease
  • Drug Delivery Systems
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use
  • Inflammation / drug therapy*
  • Inflammation / physiopathology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Immunologic Factors
  • Tumor Necrosis Factor-alpha