Mycobacterial Infections Associated with TNF-α Inhibitors

Abstract

Tumor necrosis factor (TNF) is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis and other chronic inflammatory diseases. TNF also plays a critical role in host responses to intracellular pathogens and in granuloma formation and maintenance. The TNF-α inhibitors are a class of highly effective, targeted anti-inflammatory medications in widespread use for the treatment of rheumatoid arthritis. However, evidence has accumulated since the introduction of the TNF-antagonists that they are also associated with an increased risk of granulomatous infections, including tuberculosis and non-tuberculous mycobacterial (NTM) infections. This chapter will review the literature on the role of TNF in response to mycobacterial infection, the various TNF-α inhibitors and their biological differences, and the indications for TNF-α inhibitors in the treatment of rheumatoid arthritis. We will also review the literature to date on the risk of tuberculosis associated with rheumatoid arthritis and TNFantagonist therapy. We will discuss the clinical evaluation and treatment of latent tuberculosis infection in the setting of proposed TNF-antagonist therapy, as well as the presentation and treatment of active tuberculosis. We will review the current literature on the risk of NTM disease associated with TNF-α inhibitor therapy, as well as the presentation, treatment, and prevention of NTM disease in this setting.