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  • Review Article
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The problem of choice: current biologic agents and future prospects in RA

Nature Reviews Rheumatology volume 9, pages 154–163 (2013)Cite this article

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Abstract

The introduction of biologic agents to clinical practice has had a major bearing on the treatment of patients with chronic inflammatory diseases such as rheumatoid arthritis. These drugs have the potential to improve the outcome of disease and the quality of life for patients. However, clinical criteria alone are inadequate for determining which therapy is most appropriate for an individual patient. Furthermore, why a particular drug is effective in a particular patient, or indeed in any patient, but is ineffective for other individuals, is often unknown. In this Review, we provide an overview of biologic therapies currently available for patients with rheumatoid arthritis, and discuss why certain immunological regulators represent potential targets for intervention. Current agents can be clustered into three major types: cytokine blockers, lymphocyte-targeting agents, and small-molecule inhibitors of signal transduction pathways. We differentiate among the modes of action of each of these types of therapy and consider the challenges associated with their use in clinical practice.

Key Points

  • Current interventions in rheumatoid arthritis (RA) can be classified into three major types: cytokine blockers, lymphocyte-targeting agents, and small-molecule inhibitors of signal transduction pathways

  • In the absence of reliable biomarkers, mode of action could be a useful tool in guiding choice of biologic therapy

  • Adverse effects of biologic agents are either class specific or compound specific; class-specific effects reflect the biological role of the target

  • Early-phase clinical trials in RA in the past few years have mostly focused on cytokine blockers and small-molecule inhibitors of signal transduction pathways

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Figure 1: Pathogenesis of RA: synovial and systemic inflammation.
Figure 2: Cytokine network in RA: overlap and interplay between cytokines drives synovial inflammation.
Figure 3: Cytokines and their signalling pathways: different cytokines use different intracellular signalling pathways.

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Acknowledgements

Professors Ernest Choy and Simon Jones thank Arthritis Research UK for funding support provided through the CREATE Centre (20016) and research grants (19796, 19381, 18286).

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Authors and Affiliations

  1. Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff University, Tenovus Building, Heath Park, Cardiff, CF14 4XN, UK

    Ernest H. Choy & Simon A. Jones

  2. Division of Rheumatology, Department of Medicine, Allergy and Immunology, University of California San Diego, La Jolla, San Diego, 92093-0943, CA, USA

    Arthur F. Kavanaugh

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All authors made substantial contributions to researching data for the article and writing the article. E. H. Choy handled review and editing of the article before submission.

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Correspondence to Ernest H. Choy.

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Competing interests

E. H. Choy declares that he has received research grants from and has served as a member of advisory boards and speakers bureaus for Abbott, Allergan, AstraZeneca, Boehringer Ingelheim, Chelsea Therapeutics, Chugai Pharma, Eli Lilly, GlaxoSmithKline, Jazz Pharmaceuticals, Merrimack Pharmaceutical, Merck Sharp & Dohme, Pfizer, Pierre Fabre Medicament, Roche, Schering Plough, Synovate, UCB, and Wyeth. A. F. Kavanaugh declares that he has received research grants from Abbott, Amgen, Bristol-Myers Squibb, Janssen, Pfizer, Roche, and UCB. S. A. Jones declares that he has consultancy agreements with F. Hoffmann-La Roche and NovImmune SA and has acted as an advisor for Chugai Pharma Europe and Genentech. He is also recipient of an investigator-sponsored award from F. Hoffmann-La Roche.

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Choy, E., Kavanaugh, A. & Jones, S. The problem of choice: current biologic agents and future prospects in RA. Nat Rev Rheumatol 9, 154–163 (2013). https://doi.org/10.1038/nrrheum.2013.8

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