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Tumor necrosis factor blockade and the risk of viral infection
Seo Young Kim and Daniel H. Solomon
Abstract | Tumor necrosis factor (TNF) blockers are widely used to treat rheumatoid arthritis and other chronic inflammatory diseases. Many studies have demonstrated an increased risk of opportunistic infections such as tuberculosis and fungal infection in patients treated with TNF blockers, which is thought to be related to the primary role of TNF both in host defense and in the immune response. Little is known, however, about the association between TNF blockade and the development of viral infection. Owing to the critical role of TNF in the control of viral infection, depletion of this cytokine with TNF blockers could facilitate the development or reactivation of viral infection. A number of large observational studies have found an increased risk of herpes zoster in patients receiving TNF blockers for the treatment of rheumatoid arthritis. This Review draws attention to the risk of several viral infections, including HIV, varicella zoster virus, EpsteinBarr virus, cytomegalovirus, and human papillomavirus, in patients receiving TNF-blocking therapy for chronic inflammatory conditions. In addition, implications for clinical practice and possible preventative approaches are discussed.
Kim, S. Y. & Solomon, D. H. Nat. Rev. Rheumatol. 6, 165174 (2010); published online 9 February 2010; http://www.nature.com/doifinder/10.1038/nrrheum.2009.279
Web End =doi:10.1038/nrrheum.2009.279
Introduction
Tumor necrosis factor (TNF) plays an essential part in host defense and the immune response.1 TNF receptors (TNFRs) are found on virtually all cell types, and TNF affects a variety of physiologic processes. TNF blockers are an effective treatment for several chronic inflammatory disorders, including rheumatoid arthritis (RA), and the increasingly widespread use of these agents highlights the importance of understanding their safety. Much attention has been paid to the risks of opportunistic infection (such as tuberculosis and fungal infections) associated with use of TNF blockers.2,3 Conflicting data exist, however, on the association between the use of these agents and serious infections that lead to hospitalization or mortality.46 A recent meta-analysis by Bongartz et al.7 reported that the number needed to harm for up to 1 year of therapy with infliximab or adalimumab was 59 (95% CI 39125) for serious infection.
To date, most studies have focused on the risk of bacterial and opportunistic infections, with few assessing...