Influence of anti-TNF immunogenicity on safety in rheumatic disease: a narrative review

Expert Opin Drug Saf. 2016 Dec;15(sup1):3-10. doi: 10.1080/14740338.2016.1221398.


Tumor necrosis factor-alpha (TNF-α) antagonists have been shown to be effective in the treatment of chronic inflammatory rheumatic conditions. The use of anti-TNF agents, combined with improved diagnosis, aggressive regimens and regular monitoring, have substantially improved patient outcomes. However, all biological agents are immunogenic, resulting in the formation of anti-drug antibodies (ADAs), which can neutralize drug activity leading to loss of response and potential relapse. In addition, ADAs can also cause serious adverse events such as infusion hypersensitivity reactions. Areas covered: This narrative review of studies investigating the immunogenicity and clinical safety implications of TNF antagonists confirms that structural and pharmacological differences between agents results in differences in the probabilities and outcomes of immunogenicity. Expert opinion: Anti-TNF therapies have been shown to trigger auto-immune responses such as a lupus-like syndrome. Despite the fact that all biological agents have the potential for immunogenic reactions and a number of predisposing factors have been identified, the mechanisms remain to be completely clarified and the assessment of immunogenicity and its clinical relevance is matter of discussion. There are many questions regarding immunogenicity that still need answering to better optimize anti-TNF treatment in patients with chronic inflammatory rheumatic disease.

Keywords: Anti-drug antibodies; anti-TNF agents; immunogenicity; rheumatic disease; safety.

Publication types

  • Review

MeSH terms

  • Antibodies / immunology
  • Antirheumatic Agents / adverse effects*
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use
  • Autoimmune Diseases / chemically induced
  • Drug Hypersensitivity / immunology
  • Humans
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use
  • Rheumatic Diseases / drug therapy*
  • Risk Factors
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / therapeutic use


  • Antibodies
  • Antirheumatic Agents
  • Immunologic Factors
  • Tumor Necrosis Factor-alpha