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Targeting IL-6: A review of data
  1. Josef S Smolen1,
  2. Daniel Aletaha2,
  3. Ernest H Choy3,
  4. Simon A Jones3,
  5. Tsutomu Takeuchi4,
  6. Iain McInnes5
  1. 1 Medical University of Vienna and Hietzing Hospital, Vienna, Austria
  2. 2 Department of Rheumatology, Medical University of Vienna, Vienna, Austria
  3. 3 Cardiff University, Cardiff, UK
  4. 4 Keio University Hospital, Shinjuku, Japan
  5. 5 University of Glasgow, Glasgow, UK
  1. Correspondence to Professor Josef S Smolen, Department of Internal Medicine 3, Medical University of Vienna Division of Rheumatology, Wien, 1090, Austria, josef.smolen{at}


Compounds that target interleukin (IL)−6 pathways include antibodies against the IL-6 receptor or ligand, and inhibitors of IL-6 signal transduction. The anti-IL-6 receptor (IL-6R) monoclonal antibody tocilizumab has been licensed for several years; data from multiple studies demonstrate its efficacy and tolerability in rheumatoid arthritis as monotherapy or in combination with methotrexate. In addition, another anti-IL-6R monoclonal antibody, sarilumab, has recently been approved in both the US and EU. Anti-IL-6 monoclonal antibodies include olokizumab and clazakizumab, which both have data from phase II studies, as well as sirukumab which has completed phase III trials but may not be brought to the market. Comparative data for olokizumab versus tocilizumab intervention in rheumatoid arthritis suggest no difference in efficacy between blocking the receptor or the ligand. Head-to-head studies are needed to determine whether inhibition of the Janus kinase pathway is similar in its overall efficacy to direct inhibition of IL-6 or its receptor. The IL-6 inhibitors appear to be more effective when combined with methotrexate. However, they have shown superiority to tumour necrosis factor inhibitors when used as monotherapy, and may have an advantage in patients who cannot use methotrexate or any other conventional synthetic disease modifying anti-rheumatic drug. Regarding disease activity assessment, CDAI is a more appropriate measure than DAS28 when looking at the effect of IL-6 inhibition, as these agents interfere with the acute phase response, which is heavily weighted in the formula of DAS28.

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  • 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.

  • Patient consent Not required.

  • Provenance and peer review Commissioned; externally peer reviewed.

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