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

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.