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Review
Considering new lessons about the use of IL-6 inhibitors in arthritis
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  1. Tsutomu Takeuchi1,
  2. Josef S Smolen2,
  3. Ernest H Choy3,
  4. Daniel Aletaha4,
  5. Iain McInnes5,
  6. Simon A Jones3
  1. 1 Keio University School of Medicine, Tokyo, Japan
  2. 2 Medical University of Vienna and Hietzing Hospital, Vienna, Austria
  3. 3 Cardiff University, Cardiff, UK
  4. 4 Medical University of Vienna, Vienna, Austria
  5. 5 University of Glasgow, Glasgow, UK
  1. Correspondence to Professor Tsutomu Takeuchi, Keio University Hospital, Tokyo 160-8582, Japan, tsutake{at}keio.jp

Abstract

Interleukin (IL)−6 represents one of several possible targets for the treatment of rheumatoid arthritis. Drugs targeting IL-6 can be divided into monoclonal antibodies against IL-6 itself and monoclonal antibodies against the IL-6 receptor. Both types of agent inhibit both classical signalling through membrane­-bound IL-6 receptor, and trans-signalling via formation of a complex between IL-6 and soluble IL-6 receptor. The IL-6 receptor blockers tocilizumab and sarilumab inhibit the low affinity binding of IL-6 to its receptor. The anti-IL-6 agents clazakizumab and vobarilizumab also block binding of IL-6 to the receptor, while olokizumab blocks the higher affinity interaction of the IL-6-receptor complex with gp130. The doses and dosing intervals of the biologics targeting different elements vary, but no major differences in efficacy or safety have yet been seen between the two approaches, although more studies are needed in this area. In addition to the different blocking actions of monoclonal antibodies, we consider therapeutic strategies including the timing of IL-6 blockade and the use of monotherapy versus the addition of methotrexate.

https://doi.org/10.1136/conmed-2018-000002

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    Footnotes

    • Funding This initiative is sponsored by R-Pharm through the provision of an unrestricted educational grant. R-Pharm has had no influence over the content.

    • Competing interests DA declares no conflicts. EHC reports grants from NovImmune. AG, grants and personal fees from Pfizer, grants from UCB, grants and personal fees from Roche, personal fees from Abbvie, Biogen, Bristol Myer Scripps, Chugai Pharma, Eli Lilly, Hospira, Janssen, Novartis, Regeneron, R-Pharm and Sanofi-Aventis; SAJ reports non-financial support from CESAS Medical during the conduct of the study; personal fees from CESAS Medical, Eleven Biotherapeutics, grants and personal fees from Roche Pharmaceuticals, personal fees and other from Genentech, grants and personal fees from Glaxo-Smith-Kline, Chugai Pharmaceuticals, Ferrin Pharmaceuticals, Regeneron/Sanofi, grants, personal fees and non-financial support from NovImmune AG, outside the submitted work; IM reports grants from Roche and Refereron, during the conduct of the study; grants and personal fees from Abbvie, Astra Zeneca, Celgene, GSK, Janssen, Lilly, Novartis, Pfizer, Roche, grants and personal fees from Refereron, outside the submitted work; JS reports grants from Abbvie, Astra-Zeneca, Janssen, Lilly, MSD, Pfizer, Roche, personal fees from Abbvie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Gilead, Glaxo, ILTOO, Janssen, Lilly, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB during the conduct of the study; TT reports grants, personal fees and other from Astellas Pharma Inc, Abbvie GK, Mitsubishi Tanabe Pharma Co, grants and personal fees from Bristol–Myers KK, Chugai Pharmaceutical Co Ltd, Daiichi Sankyo Co, Ltd, Pfizer Japan Inc, grants from Takeda Pharmaceutical Co, Ltd, Teijin Pharma Ltd, Asahikasei Pharma Corp, Eisai Co Ltd, AYUMI Pharmaceutical Corporation, grants and other from Taisho Toyama Pharmaceutical Co Ltd, Nipponkayaku Co Ltd, other from Astra Zeneca KK., Eli Lilly Japan KK, Novartis Pharma KK, Janssen Pharmaceutical KK, outside the submitted work; The participants/authors received personal fees for their participation in the round table.

    • Provenance and peer review Commissioned; externally peer reviewed.

    • Correction notice Minor typographical errors have been corrected since first published.