Tuberculosis and targeted synthetic or biologic DMARDs, beyond tumor necrosis factor inhibitors

Abstract

Patients with autoimmune rheumatic diseases (ARD) have an increased risk for tuberculosis (TB). The use of tumor necrosis factor inhibitors (TNFi) and glucocorticoids in these patients has been associated with an increased prevalence of latent TB reactivation. Over the last few years, several biologic disease-modifying anti-rheumatic drugs (bDMARDs), other than TNFi (e.g. rituximab, abatacept, tocilizumab, secukinumab) and targeted synthetic DMARDs (tsDMARDs) [e.g. apremilast, Janus kinase (JAK) inhibitors] have been used for the treatment of patients with ARD. For many of these drugs, especially the newer ones like JAK inhibitors or antibodies against interleukin (IL)-23, most data stem from randomized clinical trials and few are available from real life clinical experience. We sought to review the current evidence for TB risk in patients with ARD treated with tsDMARDs or bDMARDs, other than TNFi. It seems that some of these drugs are associated with a lower TB risk, indirectly compared with TNFi treatment. In fact, it appears that rituximab, apremilast and inhibitors of IL-17 and IL-23 might be safer, while more data are needed for JAK inhibitors. As seen in TNFi, risk for TB is more pronounced in TB-endemic areas. Screening for latent TB must precede initiation of any tsDMARDs or bDMARDs. The growing use of non-TNFi agents has raised the need for more real-life studies that would compare the risk for TB between TNFi and other treatment modalities for ARD. Knowledge about the TB-safety profile of these drugs could help in the decision of drug choice in patients with confirmed latent TB infection or in TB endemic areas.