The first decade of biologic TNF antagonists in clinical practice: lessons learned, unresolved issues and future directions

Curr Dir Autoimmun. 2010;11:180-210. doi: 10.1159/000289205. Epub 2010 Feb 18.


Results from clinical trials of biologic anti-TNF drugs performed in the late 1990s confirmed the biological relevance of TNF function in the pathogenesis of chronic noninfectious inflammation of joints, skin and gut, which collectively affects 2-3% of the population. Up to April 2009, more than two million patients worldwide have received the first marketed drugs, namely the monoclonal anti-TNF antibodies infliximab and adalimumab and the soluble TNF receptor etanercept. All three are equally effective in rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, but, for not clearly defined reasons, only the monoclonal antibodies are effective in inflammatory bowel disease. About 60% of patients who do not benefit from standard nonbiologic treatments for these diseases respond to TNF antagonists. Less than half of responding patients achieve complete remission of disease. Importantly, some of those patients with rheumatoid arthritis in whom long-term anti-TNF therapy induced disease remission remain disease-free after discontinuation of any kind of treatment. There are not yet reliable predictors of which patients will or will not respond on anti-TNF therapy, whereas subsequent loss of an initial clinical response occurs frequently. The spectrum of efficacy anti-TNF therapies widens to include diseases such as systemic vasculitis and sight-threatening uveitis. While paradoxical new adverse effects are recognized, i.e. exacerbation or development of new onset psoriasis, reactivation of latent tuberculosis remains the most important safety issue of anti-TNF therapies. Clinical practice guidelines and consensus statements on the criteria of introduction, duration of treatment and cessation of TNF antagonists, including safety issues, are under constant revision as data from longer periods of patient exposure accumulate. It is hoped that more efficacious drugs that will ideally target the deleterious proinflammatory properties of TNF without compromising its protective role in host defense and (auto)immunity will be available in the near future.

Publication types

  • Historical Article
  • Review

MeSH terms

  • Adult
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / history
  • Antibodies, Monoclonal / therapeutic use*
  • Arthritis, Juvenile / immunology
  • Arthritis, Juvenile / therapy
  • Arthritis, Psoriatic / immunology
  • Arthritis, Psoriatic / therapy
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / therapy
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / therapy*
  • Behcet Syndrome / immunology
  • Behcet Syndrome / therapy
  • Child
  • Clinical Trials as Topic / history
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / therapy
  • Psoriasis / immunology
  • Psoriasis / therapy
  • Spondylitis, Ankylosing / immunology
  • Spondylitis, Ankylosing / therapy
  • Tuberculosis / etiology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antibodies, Monoclonal
  • Tumor Necrosis Factor-alpha