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IL-6 inhibitors for treatment of rheumatoid arthritis: past, present, and future

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by polyarthritis. Numerous agents with varying mechanisms are used in the treatment of RA, including non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, and some biological agents. Studies to uncover the cause of RA have recently ended up scrutinizing the importance of pro-inflammatory cytokine such as tumor necrosis factor α (TNF-α) and interleukin (IL)-6 in the pathogenesis of RA. TNF-α inhibitors are increasingly used to treat RA patients who are non-responsive to conventional anti-arthritis drugs. Despite its effectiveness in a large patient population, up to two thirds of RA patients are found to be partially responsive to anti-TNF therapy. Therefore, agents targeting IL-6 such as tocilizumab (TCZ) attracted significant attention as a promising agent in RA treatment. In this article, we review the mechanism of anti-IL-6 in the treatment of RA, provide the key efficacy and safety data from clinical trials of approved anti-IL-6, TCZ, as well as six candidate IL-6 blockers including sarilumab, ALX-0061, sirukumab, MEDI5117, clazakizumab, and olokizumab, and their future perspectives in the treatment of RA.

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Acknowledgments

This study was supported by Technology Development Program of the Ministry for Food, Agriculture, Forest, and Fisheries of Republic of Korea (project number 114010031HD030).

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Correspondence to Sung Hyun Chung.

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Kim, G.W., Lee, N.R., Pi, R.H. et al. IL-6 inhibitors for treatment of rheumatoid arthritis: past, present, and future. Arch. Pharm. Res. 38, 575–584 (2015). https://doi.org/10.1007/s12272-015-0569-8

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Keywords

  • Rheumatoid arthritis
  • Interleukin-6 (IL-6)
  • Disease-modifying anti-rheumatic drugs (DMARDs)
  • Tumor necrosis factor α (TNF-α)
  • Tocilizumab (TCZ)