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Switching tumor necrosis factor inhibitors: an opinion

Nature Clinical Practice Rheumatology volume 2, pages 576–577 (2006)Cite this article

Tumour necrosis factor (TNF) inhibitors have changed the therapeutic standard of treatment for patients with rheumatoid arthritis (RA), providing substantial benefits in terms of clinical and radiographic outcomes. Three selective TNF inhibitors have been approved by the FDA for the treatment of RA: infliximab (Remicade®, Centocor, Malvern, PA); etanercept (Enbrel®, Immunex, Thousand Oaks, CA); and adalimumab (Humira®, Abbott Laboratories, Abbott Park, IL). Despite the proven efficacy of these TNF inhibitors, a significant proportion of patients demonstrate an inadequate response to one or more of these agents. Consequently, switching to a second or third TNF inhibitor has become standard practice. The question arises of whether there is a scientific or clinical rationale for switching TNF inhibitors.

At first glance, a TNF inhibitor would not be expected to show efficacy after failure of another inhibitor with the same mechanism of action. Evidence has accumulated, however, demonstrating that TNF inhibitors are similar—but not identical—in their mechanism of action. The various TNF inhibitors seem to differ in several aspects: mechanism of action, efficacy in diseases other than RA, and safety profile. Monoclonal antibodies, such as infliximab and adalimumab, differ from the fusion protein etanercept in their pharmacokinetics, avidity and affinity to TNF, their ability to bind membrane-bound TNF, and their ability to induce apoptosis.1 Unlike infliximab and adalimumab, etanercept is capable of binding lymphotoxin β and has not been shown to induce neutralizing antibodies. Infliximab also differs from adalimumab in terms of pharmacokinetics and dosing regimen.

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Authors and Affiliations

  1. University of Toronto,

    Edward C Keystone

  2. Mount Sinai Hospital,

    Edward C Keystone

  3. Canadian Rheumatology Research Consortium, Toronto, Ontario, Canada

    Edward C Keystone

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  1. Edward C Keystone
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Correspondence to Edward C Keystone.

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Competing interests

The author has conducted research for the following companies: Amgen, Bristol-Myers Squibb, Centocor Inc, Hoffman-La Roche Ltd (Canada), Abbott laboratories, Novartis, Schring Plough Inc., Targeted Genetics, Therakos, Wyeth Pharmaceuticals.

The author has acted as a Consultant or a member of the Advisory Board for the following companies: Abbott Laboratories, Amgen, Aventis Pharma, Bristol-Myers Squibb, Celltech, Centocor Inc., Genentech, Hoffman La-Roche Ltd, Schring Plough Inc., Targeted Genetics, Wyeth Ayerst, Genentech.

The author is a Speaker for the following companies: Abbott Laboratories, Amgen, Aventis Pharma, Centocor Inc., Genentech, hoffman-La Roche Ltd, Schering Plough Inc, Wyeth.

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Keystone, E. Switching tumor necrosis factor inhibitors: an opinion. Nat Rev Rheumatol 2, 576–577 (2006). https://doi.org/10.1038/ncprheum0339

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