title: Antagonists of TNF action: clinical experience and new developments.
abstract: BACKGROUND
  TNF is a central mediator of inflammation and key target for intervention in inflammatory diseases such as rheumatoid arthritis, psoriasis and Crohn's disease. The four at present approved protein therapeutics directly target TNF and inhibit binding to its two TNF receptors. Treatment with TNF antagonists results in significant clinical responses and is generally well tolerated.
  
  
  OBJECTIVE
  Ten years of clinical experience with 1 million patients treated also revealed the limits of the available antagonists and potential therapy-associated risks, foremost being tuberculosis reactivation, but also neurologic and hematologic events, and even malignancies. These findings ask for improvement of established therapies.
  
  
  METHODS
  We here review published literature on strategies interfering with TNF action and provide an overview of the now approved antagonists of TNF action as well as new reagents under development.
  
  
  CONCLUSIONS
  Clinical experience with approved TNF antagonists shows that there is a demand for minimizing risks associated with persistent blocking of TNF action. With new TNF pathway-targeting reagents and new concepts based on receptor-selective intervention under development, it is foreseeable that efficacy and safety will be further improved and that TNF-targeting strategies will be exploited in further inflammatory and other diseases, including metabolic diseases and cancer.
authors.affiliation: Universität Stuttgart, Institut für Zellbiologie und Immunologie, Allmandring 31, 70569 Stuttgart, Germany +49 711 68566989 ; +49 711 68567484 ; roland.kontermann@izi.uni-stuttgart.de.
authors.forename: Roland E
authors.initials: RE
authors.lastname: Kontermann
authors.forename: Peter
authors.initials: P
authors.lastname: Scheurich
authors.forename: Klaus
authors.initials: K
authors.lastname: Pfizenmaier