Review Article | Published:

Risk and prevention of tuberculosis and other serious opportunistic infections associated with the inhibition of tumor necrosis factor

Nature Clinical Practice Rheumatology volume 2, pages 602610 (2006) | Download Citation



Tumor necrosis factor (TNF) is a proinflammatory cytokine that has a key role in the pathogenesis of a variety of autoimmune diseases—including rheumatoid arthritis—and is an important constituent of the human immune response to infection. At present, three anti-TNF agents are approved (in the US and elsewhere) to treat selected autoimmune diseases: infliximab, etanercept, and adalimumab. These biologic agents have been associated with a variety of serious and 'routine' opportunistic infections; however, differences exist in the mechanisms of action of these agents that might confer variation in their associated risks of infection. From a public-health standpoint, the development of active tuberculosis in some patients who receive anti-TNF therapy is a matter of serious concern. Tuberculosis in such patients frequently presents as extrapulmonary or disseminated disease, and clinicians should be vigilant for tuberculosis in any patient taking anti-TNF therapy who develops fever, weight loss, or cough. To prevent the reactivation of latent tuberculosis infection during anti-TNF therapy, clinicians should screen all patients for tuberculosis, and begin treatment if latent infection is found, before anti-TNF therapy is initiated. Specific tuberculosis screening and treatment strategies vary between geographical regions and are reviewed in this document. The screening strategies employed in Europe and North America have reduced the occurrence of anti-TNF-associated tuberculosis and are clearly to be recommended, but the role of screening in the prevention of other opportunistic (e.g. fungal) infections is far less certain.

Key points

  • A variety of infections have been reported in association with the use of tumor necrosis factor (TNF) antagonists; among these, the development of tuberculosis is of serious concern

  • Clinicians should be vigilant for tuberculosis in any patient taking anti-TNF therapy who develops fever, constitutional symptoms, or cough; in this setting, tuberculosis often manifests as extrapulmonary or disseminated disease

  • Screen patients for risk factors for Mycobacterium tuberculosis and test them for infection before initiating immunosuppressive therapies, including TNF antagonists

  • Latent tuberculosis infection should be treated in accordance with local guidelines

  • Interferon gamma release assays might also be used to test for latent tuberculosis infection, although experience of using these assays in immunosuppressed populations is limited

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The author gratefully acknowledges the assistance of Dr Jeff Siegel who provided a critical review of this manuscript.

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  1. KL Winthrop is an Assistant Professor in the Division of Infectious Diseases, Department of Medicine, and in the Department of Public Health and Preventive Medicine, Oregon Health and Science University, Portland, OR, USA.

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The author declares no competing financial interests.

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