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

Andrea Matucci, Daniele Cammelli, Fabrizio Cantini, Delia Goletti, Anna Valentina De Marino, Giuseppe Maria Milano, Raffaele Scarpa, Giuliano Tocci, Enrico Maggi, Alessandra Vultaggio

Research output: Contribution to journalArticlepeer-review


INTRODUCTION: 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.

Original languageEnglish
Pages (from-to)3-10
Number of pages8
JournalExpert Opinion on Drug Safety
Issue numbersup1
Publication statusPublished - Dec 2016


  • Antibodies
  • Antirheumatic Agents
  • Autoimmune Diseases
  • Drug Hypersensitivity
  • Humans
  • Immunologic Factors
  • Rheumatic Diseases
  • Risk Factors
  • Tumor Necrosis Factor-alpha
  • Journal Article
  • Review


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