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Anti-TNF biologic agents: still the therapy of choice for rheumatoid arthritis

Nature Reviews Rheumatology volume 5, pages 578–582 (2009)Cite this article

Abstract

Cytokines such as tumor necrosis factor (TNF) are expressed at high levels in rheumatoid joint tissue, where they contribute significantly to inflammation and articular destruction. TNF was the first cytokine to be fully validated as a therapeutic target for rheumatoid arthritis (RA). In nearly a decade since anti-TNF agents—such as infliximab, etanercept and adalimumab—were launched as the first biologic therapies to be licensed for RA, much has been learnt about how and when in the disease course this class of drug can be used to achieve optimal therapeutic benefit. Other cytokine targets, such as interleukin (IL)-6 or IL-1, have also been validated and several are in the process of being tested. However, TNF is likely to remain the preferred target of first-line biologic therapy for the foreseeable future as, in populations with active RA despite ongoing, nonbiologic, DMARD therapy, biologic inhibition of either IL-6 or IL-1 demonstrates no obviously superior outcomes to TNF blockade. Furthermore, new approaches to blockade of signaling mediated by bioactive TNF might have the potential to generate higher-magnitude clinical responses than are currently elicited.

Key Points

  • Tumor necrosis factor (TNF) was the first cytokine to be fully validated as a therapeutic target for rheumatoid arthritis (RA)

  • Combination therapy with an anti-TNF biologic agent plus methotrexate halts progression of joint damage in the majority of patients with RA, irrespective of the extent of destruction on baseline radiography

  • Studies of patients with early RA receiving anti-TNF therapy show particularly favorable outcomes; high proportions of patients achieve sustained low disease activity or remission

  • One of the major pitfalls of biologic TNF inhibition is the occurrence of infectious complications (common or opportunistic)

  • Other shortcomings of current anti-TNF biologics include high costs, inadequate numbers of treated patients achieving sustained, high-magnitude responses or remission and secondary loss of efficacy over time

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Figure 1: The biologic actions of TNF that are known to be relevant in the pathogenesis of RA.

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Authors and Affiliations

  1. Kennedy Institute of Rheumatology Division, Imperial College, London, UK

    Peter C. Taylor & Marc Feldmann

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  1. Peter C. Taylor
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  2. Marc Feldmann
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Correspondence to Peter C. Taylor.

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Peter C. Taylor declares that he has been involved in speakers' bureaux (honoraria) and acted as a consultant for UCB, Bristol-Myers Squibb, Roche, Centocor JNJ, Schering-Plough, Wyeth and Abbott.

Marcus Feldmann declares that he has acted as a consultant for Abbott; has acted as a consultant for, received grant or research support from, is a shareholder in, and a holds a patent from Centocor JNJ; has acted as a consultant for, and received grant or research support from, Wyeth; has acted as a consultant for, and is a shareholder in, Schering-Plough, has acted as a consultant for Amgen; has acted as a consultant for, and received grant or research support from, Roche; and has acted as a consultant for UCB.

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Taylor, P., Feldmann, M. Anti-TNF biologic agents: still the therapy of choice for rheumatoid arthritis. Nat Rev Rheumatol 5, 578–582 (2009). https://doi.org/10.1038/nrrheum.2009.181

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