title: 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.
authors: Department of Pharmacology and Clinical Pharmacy, College of Pharmacy, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors: Go Woon
authors: GW
authors: Kim
authors: Na Ra
authors: NR
authors: Lee
authors: Ryo Han
authors: RH
authors: Pi
authors: Yee Seul
authors: YS
authors: Lim
authors: Yu Mi
authors: YM
authors: Lee
authors: Jong Min
authors: JM
authors: Lee
authors: Hye Seung
authors: HS
authors: Jeong
authors: Sung Hyun
authors: SH
authors: Chung
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic; D005544:Forecasting; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016896:Treatment Outcome; D000093242:Interleukin-6 Inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors; C508600:IL6 protein, human; C000604955:clazakizumab; C568922:sirukumab; C502936:tocilizumab