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Baseline levels of soluble interleukin-6 receptor predict clinical remission in patients with rheumatoid arthritis treated with tocilizumab: implications for molecular targeted therapy
  1. Naoshi Nishina1,
  2. Jun Kikuchi1,
  3. Misato Hashizume2,
  4. Keiko Yoshimoto1,
  5. Hideto Kameda1,3,
  6. Tsutomu Takeuchi1
  1. 1 Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
  2. 2 Product Research Department, Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Gotemba, Japan
  3. 3 Division of Rheumatology, Department of Internal Medicine, School of Medicine, Toho University, Tokyo, Japan
  1. Correspondence to Dr Naoshi Nishina, Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; nnishina{at}

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Interleukin-6 (IL-6) is a monomeric protein that binds to either soluble or membrane-bound IL-6 receptors (IL-6R)1 ,2 Tocilizumab, a humanised anti-IL-6R monoclonal antibody, binds to soluble IL-6R (sIL-6R) and membrane-bound IL-6R, blocking signal transduction pathways through competitive inhibition of IL-6 binding.3 We have previously demonstrated that baseline plasma tumour necrosis factor (TNF) levels are associated with the clinical response to infliximab, anti-TNF monoclonal antibody binding to soluble and membrane-bound TNF.4 Therefore, it is tempting to speculate that baseline serum levels of sIL-6R, rather than those of IL-6, are associated with clinical response to tocilizumab in patients with rheumatoid arthritis (RA). To test this hypothesis, we analysed serum levels of IL-6 and sIL-6R before tocilizumab treatment in our institution and evaluated their association with clinical remission.

Consecutive patients with RA in our institution who commenced 8 mg/kg tocilizumab treatment every 4 weeks as the first biologic agent between March 2010 and April 2012 were included. At baseline, serum levels of IL-6 and sIL-6R were measured by electrochemiluminescence assay with the Ultra-Sensitive Kit (Meso Scale …

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  • Contributors All the authors evaluated the study results, interpreted the data and suggested additional analyses. All authors contributed to the development and critical review of manuscript and approved the final version.

  • Funding This study was supported by Chugai Pharmaceutical Co, Ltd.

  • Competing interests MH is an employee of Chugai Pharmaceutical Co, Ltd. TT has received consulting fees, speaking fees, honoraria and/or research grant support from Abbott Japan Co; Abbvie GK; Asahi Kasei Pharma Corp; Astellas Pharma Inc; Astra-Zeneca KK; Bristol-Myers KK; Chugai Pharmaceutical Co, Ltd; Daiichi-Sankyo Co; Eisai Co; Eli-Lilly Japan KK; Janssen Pharmaceutical KK; Mitsubishi Tanabe Pharma Co; Novartis Pharma KK; Pfizer Japan Inc; Sanofi-aventis KK; Santen Pharmaceutical Co, Ltd; Taisho Toyama Pharmaceutical Co, Ltd; Takeda Pharmaceutical Co, Ltd; and Teijin Pharma Ltd.

  • Patient consent Obtained.

  • Ethics approval The ethics committee at Keio University School of Medicine.

  • Provenance and peer review Not commissioned; externally peer reviewed.