**1. Introduction**

70 Rheumatoid Arthritis – Treatment

Tsuru, T, Suzaki, M, Yoshio, N, Mima, T, Nakashima, H, Amamoto, T, Aoki, C, Uchino, A,

van Vollenhoven, R.F, Keystone, E.C, Furie, R, Blesch, A, Wang, C, & Curtis, J.R. (2009).

van Vollenhoven, R.F, Scali, J, Curtis, J.R, Krasnow, J, Vernon, E, & Alten, R. (2010). Safety of

Welsh, K.J, Abbott, A.N, Hwang, S.A, Indrigo, J, Armitige, L.Y, Blackburn, M.R, Hunter,

Yamanaka, H, Nishimoto, N, Inoue, E, Hara, M, Tomatsu, T, & Kamatani, N. (2007).

Yamanaka, H, Tanaka, Y, Inoue, E, Hoshi, D, Momohara, S, Hanami, K, Yunoue, N, Saito, K,

II, pp. 339, ISSN 0003-4967

Suppl 10, pp. 1613, ISSN 0004-3591

No. Suppl 3, pp. 544, ISSN 0003-4967

Suppl II, pp. 122ISSN 0003-4967

2, pp. 122-133, ISSN 1439-7609

Vol. 154, No. Pt 6, pp. 1813-1824, ISSN 1350-0872

Terao, K, Kakehi, T, & Nishimoto, N. (2008). Immune response to influenza vaccine in patients during the treatment with tocilizumab - comparison with conventional DMARDs and TNF inhibitors. *Annals of the Rheumatic Diseases*, Vol. 67, No. Suppl

Gastrointestinal safety in patients with rheumatoid arthritis treated with tocilizumab: data from Roche clinical trials. *Arthritis and Rheumatism*, Vol. 60, No.

tocilizumab in patients with rheumatoid arthritis: analysis of median of 2.6 years of treatment in long-term extension studies. *Annals of the Rheumatic Diseases*, Vol. 69,

R.L, & Actor, J.K. (2008). A role for tumour necrosis factor-alpha, complement C5 and interleukin-6 in the initiation and development of the mycobacterial cord factor trehalose 6,6'-dimycolate induced granulomatous response. *Microbiology*,

Incidence of malignancies in Japanese Rheumatoid arthritis patients treated with tocilizumab in comparison to those in an observational cohort of Japanese patients and a Japanese population database. *Annals of the Rheumatic Diseases*, Vol. 66, No.

Amano, K, Kameda, H, & Takeuchi, T. (2011). Efficacy and tolerability of tocilizumab in rheumatoid arthritis patients seen in daily clinical practice in Japan: results from a retrospective study (REACTION study). *Mod Rheumatol*, Vol. 21, No. 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.
