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

ABSTRACT

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.

KEYWORDS:

• Anti-drug antibodies
• anti-TNF agents
• immunogenicity
• safety
• rheumatic disease

Article highlights

• All biological agents are immunogenic resulting in formation of anti-drug antibodies, which in addition to neutralizing drug activity leading to loss of response and potential relapse, can also cause serious adverse events such as allergic infusion reactions.

• Structural and pharmacological differences among the anti-TNFs result in differences in propensity for and outcomes of immunogenicity.

• Infliximab is associated with the highest rates of immunogenicity resulting predominantly in allergic infusions reactions.

• Thromboembolic events have been reported with adalimumab and (rarely) etanercept and lupus-like symptoms have been reported with golimumab and infliximab.

• There are many questions regarding immunogenicity with long-term anti-TNF therapy in patients with chronic inflammatory rheumatic disease, including the mechanisms involved, reliable assessment of immunogenicity, and optimal regimens.

This box summarizes key points contained in the article.

Acknowledgments

We are grateful to Antonio Spadaro who participated in the early phase of this study. Unfortunately, he passed away before seeing the completion of the review.

Declaration of interest

Valentina Marino is an employee of Pfizer Italia. Health Publishing & Services Srl provided editorial assistance for the preparation of this article. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This article is part of a supplement supported by an unrestricted grant from Pfizer Italia.