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Nonresponse to tumor necrosis factor antagonists—is there any point in re-treatment?

Nature Clinical Practice Rheumatology volume 2, pages 288–289 (2006)Cite this article

The introduction of tumor necrosis factor (TNF) antagonists has transformed expectations of the management of rheumatoid arthritis (RA). Three licensed TNF antagonists exist: infliximab, etanercept, and adalimumab. All have demonstrated comparable clinical efficacy, although head-to-head studies have not been performed. Despite the successes of these agents, heterogeneity of response and treatment failure has been observed in up to 40% of patients,1 calling into question the use of alternative TNF-blocking therapies in patients who have failed treatment.

While conferring a TNF-antagonist action, the mechanism of action differs between available anti-TNF agents:2 for example, infliximab and adalimumab bind both soluble and membrane-bound TNF; etanercept binds soluble, and, to a lesser degree, membrane-bound TNF, and also lymphotoxin-α (LT-α). Although infliximab binds both monomeric and trimeric (bioactive) TNF, it is postulated to cause cell lysis via antibody-dependent, cell-mediated cytotoxicity or via complement activation.3

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References

  1. Lipsky PE et al. (2000) Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med 343: 1594–1602

    Article  CAS  Google Scholar 

  2. Scallon B et al. (2002) Binding and functional comparisons of two types of tumor necrosis factor antagonists. J Pharmacol Exp Ther 301: 418–426

    Article  CAS  Google Scholar 

  3. Scallon BJ et al. (1995) Chimeric anti-TNF-alpha monoclonal antibody cA2 binds recombinant transmembrane TNF-alpha and activates immune effector functions. Cytokine 7: 251–259

    Article  CAS  Google Scholar 

  4. Buch MH et al. (2005) C-reactive protein as a predictor of infliximab outcome in patients with rheumatoid arthritis: defining subtypes of non-response and subsequent response to etanercept. Arthritis Rheum 51: 42–48

    Article  Google Scholar 

  5. van Vollenhoven R et al. (2003) Treatment with infliximab (Remicade) when etanercept (Enbrel) has failed or vice versa: data from the STURE registry showing that switching tumour necrosis factor alpha blockers can make sense. Ann Rheum Dis 62: 1195–1198

    Article  CAS  Google Scholar 

  6. Buch MH et al. (2003) Do patients with rheumatoid arthritis with high disease activity on infliximab demonstrate an improvement on etanercept? Ann Rheum Dis 62: S237

    Google Scholar 

  7. Buch MH et al. (2004) True infliximab resistance in rheumatoid arthritis: a role for lymphotoxin-alpha? Ann Rheum Dis 63: 1344–1346

    Article  CAS  Google Scholar 

  8. Furst D et al. (2005) Infliximab provides additional clinical and radiographic benefits in RA patients who have an inadequate response to etanercept. Ann Rheum Dis 64: S0058

    Article  Google Scholar 

  9. Buch MH et al. (2005) Types of previous infliximab non-response in rheumatoid arthritis determines subsequent response to adalimumab. Arthritis Rheum 52: S882

    Google Scholar 

  10. Burmester GR et al. (2005) Adalimumab (Humira®) is effective in patients who have previously been treated with TNF-antagonists (etanercept and/or infliximab) in widespread clinical practice: 12 week outcomes in the REACT trial. Ann Rheum Dis 64 (Suppl 3): S423

    Google Scholar 

  11. Feldmann M (2002) Development of anti-TNF therapy for rheumatoid arthritis. Nature Rev Immunol 2: 364–371

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Professor of Rheumatology and the Lead Clinician,

    Maya H Buch & Paul Emery

  2. Specialist Registrar in Rheumatology, at the Leeds Teaching Hospital, Leeds, UK

    Maya H Buch & Paul Emery

Authors
  1. Maya H Buch
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  2. Paul Emery
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Correspondence to Paul Emery.

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Competing interests

P Emery has assisted in clinical trials and given expert advice to all major rheumatology companies.

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Buch, M., Emery, P. Nonresponse to tumor necrosis factor antagonists—is there any point in re-treatment?. Nat Rev Rheumatol 2, 288–289 (2006). https://doi.org/10.1038/ncprheum0210

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