Elsevier

Autoimmunity Reviews

Volume 7, Issue 1, November 2007, Pages 35-41
Autoimmunity Reviews

Biological and clinical effects of anti-TNFα treatment

https://doi.org/10.1016/j.autrev.2007.03.003Get rights and content

Abstract

Tumor necrosis factor alpha (TNFα) is implicated in the pathogenesis of many chronic inflammatory diseases such as rheumatoid arthritis (RA), psoriasis and psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn's disease, ulcerative colitis and uveitis. The availability of new pharmacological agents (infliximab, etanercept, adalimumab), able to selectively block the TNFα, has recently offered new opportunity for the treatment of these diseases. TNFα antagonists are different in the mechanism of action and are all effective agents in the treatment of RA and several chronic inflammatory diseases as a large number of controlled clinical trials have shown. Among biological effects of TNFα antagonists, the production of autoantibodies has been emphasized. This phenomenon is not correlated with the disease background, since anti-nuclear antibodies (ANA) and anti-double stranded-DNA antibodies (anti-dsDNA) induction is observed in RA as well as in spondyloarthritis (SpA) patients. Nonetheless, recent studies had reported a significant reduction in the serum titre of rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibodies (anti-CCP) during anti-TNFα therapy. The TNFα antagonists represent a significant advance in the therapy of active RA and other chronic inflammatory diseases. However, they have distinct biological, clinical, and pharmacological properties that must be considered when selecting a drug for therapy.

Section snippets

TNFα antagonists are different in the mechanism of action and they are efficacious in the treatment of chronic inflammatory diseases

Infliximab and adalimumab are both anti-TNFα monoclonal, the first being a chimeric human-murine antibody, while the latter a fully human antibody. Both agents are specific for TNFα; they do not bind lymphotoxin α (LTα). Etanercept is a fusion protein made up of the extracellular domain of the p75 TNF receptor (CD120b) and the hinge and Fc domains of human IgG1.

Infliximab binds soluble and cell-surface TNFα [1]; each infliximab molecule is capable of binding two TNF molecules, and up to three

TNFα antagonists are able to induce the synthesis of autoantibodies

Among biological effects of TNF antagonists, the production of new autoantibodies has been emphasized. Several studies focused on the appearance of autoantibodies in the RA patients sera after anti-TNF treatment.

The pathogenesis of these antibodies is not fully understood. It seems these antibodies are not correlated with the disease background, since ANA and anti-dsDNA induction is observed in RA as well as in SpA patients. Several possible explanations for the induction of ANA during anti-TNF

TNFα antagonists are able to reduce the synthesis of autoantibodies

Recent studies have reported, after 3–12 months of anti-TNFα treatment in RA patients, a significant reduction in the serum titre of RF and anti-CCP in correlation with clinical improvement [35], [36], [37], [32]. Other studies showed a reduction in IgM-RF titres alone, arguing that RF and anti-CCP antibodies are independent autoantibody systems in RA [23]. These conflicting results may be due, at least in part, to the different periods of follow-up and to the methods used to measure the

Conclusion

The TNF antagonists represent a significant advance in the therapy of active RA and others chronic inflammatory diseases. However, they have distinct biological, clinical, and pharmacological properties, that must be considered when selecting a drug for therapy. Differences in the efficacy profiles of anti-TNF are likely related to the pathophysiology of the diseases (e.g. role of lymphotoxin) as well as drug characteristics (e.g. dosing, pharmacokinetics, immunogenicity, ability to block

Acknowledgement

This work has been supported by a grant from MIUR-PRIN; Grandi Progetti d'Ateneo, La Sapienza; Fondazione U. Di Mario.

Take-home messages

  • TNFα antagonists are efficacious in the treatment of many chronic inflammatory diseases, as demonstrated in several randomized clinical trials and open label experience, showing clinical and radiological improvement in treated patients. The different mechanism of action between monoclonal antibodies (infliximab and adalimumab) and soluble receptor (etanercept)

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