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

• Published in: Archives of pharmacal research Vol. 38; no. 5; pp. 575 - 584
• Main Authors: Kim, Go Woon, Lee, Na Ra, Pi, Ryo Han, Lim, Yee Seul, Lee, Yu Mi, Lee, Jong Min, Jeong, Hye Seung, Chung, Sung Hyun
• Format: Journal Article
• Language: English
• Published: Seoul Pharmaceutical Society of Korea 01.05.2015; 대한약학회
• Subjects: Animals; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized - pharmacology; Antibodies, Monoclonal, Humanized - therapeutic use; Antirheumatic Agents - pharmacology; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - diagnosis; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - metabolism; clinical trials; Clinical Trials as Topic; Forecasting; Humans; interleukin-6; Interleukin-6 - antagonists & inhibitors; Interleukin-6 - metabolism; Medicine; nonsteroidal anti-inflammatory agents; pathogenesis; patients; Pharmacology/Toxicology; Pharmacy; Review; rheumatoid arthritis; therapeutics; Treatment Outcome; tumor necrosis factor-alpha; 약학; Tumor necrosis factor α (TNF-α); Interleukin-6 (IL-6); Disease-modifying anti-rheumatic drugs (DMARDs); Rheumatoid arthritis; Tocilizumab (TCZ)
• ISSN: 0253-6269; 1976-3786; 1976-3786
• DOI: 10.1007/s12272-015-0569-8

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.