The molecular level influence of tocilizumab administration in patients with systemic sclerosis

• Project/Area Number: 24591444
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Osaka University
• Principal Investigator: SHIMA Yoshihito 大阪大学, 医学(系)研究科(研究院), 助教 (90362706)
• Co-Investigator(Kenkyū-buntansha): TANAKA Toshio 大阪大学, 大学院医学系研究科抗体医薬臨床応用学, 寄附講座教授 (40273651)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 全身性強皮症 / サイトカイン / interleukin-6 / 抗IL-6受容体抗体 / tocilizumab / 生物学的製剤

Outline of Final Research Achievements

Interleukin-6 (IL-6) is thought to play a part of role in the pathogenesis of systemic sclerosis. To know the influence of anti-interleukin 6 receptor antibody tocilizumab (TCZ) which can inhibit the function of IL-6 to the patients with systemic sclerosis, we conduct a clinical trial using TCZ. We analyzed 23 kinds of cytokines, chemokines in the sera of the entry patients to know the effect of TCZ. The patients who showed decrease of skin score presented transiently augmentations of IL-6, IL-8, IL-1beta, and MIP-1alfa. They also presented decrease of IL-10、IL-12、and IL-9 parallel to decrease of their skin score. We have not found out the correlation between the IL-6 level before initiating TCZ and the changes of skin score. The decreasing cytokines may be noteworthy to make a new treatment strategy.

Research Products

• [Journal Article] Expansion of range of joint motion following treatment of systemic sclerosis with tocilizumab. (2014)
  • Author(s): Shima Y, Hosen N, Hirano T, Arimitsu J, Nishida S, Hagihara K, Narazaki M, Ogata A, Tanaka T, Kishimoto T, Kumanogoh A
  • Journal Title: Modern Rheumatology Volume: 未定 Issue: 1 Pages: 134-137
  • DOI: 10.3109/14397595.2013.874749
  • Peer Reviewed
• [Journal Article] Tocilizumab for the Treatment of Patients With Refractory Takayasu Arteritis (2013)
  • Author(s): Nakaoka Y, Higuchi K, Arita Y, Otsuki M, Yamamoto K, Hashimoto-Kataoka T, Yasui T, Ikeoka K, Ohtani T, Sakata Y, Shima Y, Kumanogoh A, Yamauchi-Takihara K, Tanaka T, Kishimoto T, Komuro I
  • Journal Title: International Heart Journal Volume: 54 Issue: 6 Pages: 405-411
  • DOI: 10.1536/ihj.54.405
  • NAID: 130003383361
  • ISSN: 1349-2365, 1349-3299
  • Peer Reviewed
• [Journal Article] Retention of tocilizumab and anti-tumour necrosis factor drugs in the treatment of rheumatoid arthritis. (2013)
  • Author(s): Hishitani Y, Ogata A, Shima Y, Hirano T, Ebina K, Kunugiza Y, Shi K, Narazaki M, Hagihara K, Tomita T, Yoshikawa H, Tanaka T, Kumanogoh A
  • Journal Title: Scandinavian Journal of Rheumatology Volume: 42 Issue: 4 Pages: 253-259
  • DOI: 10.3109/03009742.2012.762037
  • Peer Reviewed
• [Journal Article] Expansion of range of joint motion following treatment of systemic sclerosis with tocilizumab. (2013)
  • Author(s): Shima Y, Hosen N, Hirano T, Arimitsu J, Nishida S, Hagihara K, Narazaki M, Ogata A, Tanaka T, Kishimoto T, Kumanogoh A
  • Journal Title: Modern Rheumatology Volume: In press
  • DOI: 10.1007/s10165-013-0855-6
  • Peer Reviewed
• [Journal Article] Blockade of interleukin-6 receptor alleviates disease in mouse model of scleroderma (2012)
  • Author(s): Kitaba S, Murota H, Terao M, Azukizawa H, Terabe F, Shima Y, Fujimoto M, Tanaka T, Naka T, Kishimoto T, Katayama I
  • Journal Title: Am J Pathol Volume: 180(1) Issue: 1 Pages: 165-176
  • DOI: 10.1016/j.ajpath.2011.09.013
  • Peer Reviewed
• [Presentation] ヒト型化抗IL-6受容体抗体（トシリズマブ）の全身性強皮症に対する影響を探索する無作為比較多施設試験 (2015)
  • Author(s): 嶋 良仁、桑名正隆、川口鎮司
  • Organizer: 第59回日本リウマチ学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-04-23 – 2015-04-25
• [Presentation] ヒト型化抗IL-6受容体抗体(tocilizumab)の全身性強皮症に対する影響を探索する無作為比較多施設試験 (2015)
  • Author(s): 嶋 良仁
  • Organizer: 第18回強皮症研究会議
  • Place of Presentation: 東京
  • Year and Date: 2015-01-17
• [Presentation] 全身性強皮症患者に対するヒト皮膚用Vesmeterによる評価
  • Author(s): 嶋 良仁
  • Organizer: 第17回全身性強皮症研究会議
  • Place of Presentation: 大正製薬本社2号館
• [Book] Systemic Sclerosis: Basic and Translational (2015)
  • Author(s): Takehara K, Kuwana M, Fujimoto M, Ihn H, Yamamoto T, Tuchiya N, Kawaguchi Y, Shima Y, Jinnin M, Motegi S, Matsushita T, Asano Y, Hasegawa M, Hamaguchi Y
  • Publisher: Springer
• [Book] Novel Insights into Systemic Sclerosis ManagementNovel Insights into Systemic Sclerosis Management: Management: Therapeutic potentials of IL-6 inhibition for systemic sclerosis. (2013)
  • Author(s): Shima Y, Kuwana M
  • Total Pages: 10
  • Publisher: Future Medicine
• [Book] IL-6 Targeting Strategy for Various Immune-Mediated Diseases other than Rheumatoid Arthritis: An Update Review Chapter 2, "Interleukin-6: Genetics, Clinical Applications and Role in Disease (2013)
  • Author(s): Tanaka T, Ogata A, Shima Y, Narazaki M, Kumanogoh A, Kishimoto T
  • Total Pages: 49
  • Publisher: Nova Science Publishers Inc.