Factors to identify rapid progressive joint destruction and to predict effectiveness of drugs in rheumatoid arthritis

• Project/Area Number: 23791120
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Keio University
• Principal Investigator: KANEKO Yuko 慶應義塾大学, 医学部, 助教 (60317112)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 関節リウマチ / 関節破壊 / 薬剤効果予測

Research Abstract

The aim of this study was to identify factors to predict rapid progressive joint destruction and effectiveness of drugs in rheumatoid arthritis. We demonstrated a significant (p<0.001) reduction of plasma IL-6 but not TNFa during MTX treatment, and that the post-treatment IL-6 level was a strong indicator of radiographic progression. We showed that TRAF1 (+16860A/G) was associated with the clinical response to anti-TNF treatment. Moreover, we showed the population of CD14+CD16+ increased in peripheral blood, and they were related with the rapid radiological progression. Our study indicated the possibility that those factors may enable us to implement personalized treatment.

Research Products

• [Journal Article] Tocilizumab is clinically, functionally, and radiographically effective and safe either with or without low-dose methotrexate in active rheumatoid arthritis patients with inadequate responses to DMARDs and/or TNF inhibitors : A single-center retrospective cohort study (KEIO-TCZ study) at week 52 (2014)
  • Author(s): Izumi K, Kaneko Y, Yasuoka H, Seta N, Kameda H, Kuwana M, Takeuchi T
  • Journal Title: Mod Rheumatol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Distinct arthropathies of the hands in patients with anti-aminoacyl tRNA synthetase antibodies : usefulness of autoantibody profiles in classifying patients (2014)
  • Author(s): Kaneko Y, Hanaoka H, Hirakata M, Takeuchi T, Kuwana M
  • Journal Title: Rheumatology (Oxford) Volume: (in press)
  • Peer Reviewed
• [Journal Article] A single nucleotide polymorphism of TRAF1 predicts the clinical response to anti-TNF treatment in Japanese patients with rheumatoid arthritis (2014)
  • Author(s): Nishimoto T, Seta N, Anan R, Yamamoto T, Kaneko Y, Takeuchi T, Kuwana M
  • Journal Title: Clin Exp Rheumatol Volume: 32 Pages: 211-7
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/24321457
  • Peer Reviewed
• [Journal Article] American College of Rheumatology/European League Against Rheumatism remission criteria for rheumatoid arthritis maintain reliable performance when evaluated in 44 joints. (2013)
  • Author(s): Kaneko Y, Kondo H, Takeuchi T
  • Journal Title: J Rheumatol Volume: 40 Issue: 8 Pages: 1254-1258
  • DOI: 10.3899/jrheum.130166
  • Peer Reviewed
• [Journal Article] Reduction of plasma IL-6 but not TNF-αby methotrexate in patients with early rheumatoid arthritis : a potential biomarker for radiographic progression (2013)
  • Author(s): Nishina N, Kaneko Y, Kuwana M, Hanaoka H, Kameda H, Mikami S, Takeuchi T
  • Journal Title: Clin Rheumatol Volume: 32 Issue: 11 Pages: 1661-6
  • DOI: 10.1007/s10067-013-2309-0
  • Peer Reviewed
• [Journal Article] A single nucleotide polymorphism of TRAF1 predicts the clinical response to anti-TNF treatment in Japanese patients with rheumatoid arthritis. (2013)
  • Author(s): Nishimoto T, Seta N, Anan R, Yamamoto T, Kaneko Y, Takeuchi T, Kuwana M.
  • Journal Title: Clin Exp Rheumatol Volume: Epub
  • Peer Reviewed
• [Journal Article] Discordance in global assessments between patient and estimator in patients with newly diagnosed rheumatoid arthritis: associations with progressive joint destruction and functional disorder (2013)
  • Author(s): Yuko Kaneko, Masataka Kuwana, Harumi Kondo, Tsutomu Takeuchi
  • Journal Title: J Rheumatol Volume: Epub
  • Peer Reviewed
• [Journal Article] Structural damages disturb functional improvement in patients with rheumatoid arthritis treated with etanercept (2012)
  • Author(s): Tanaka Y, Yamanaka H, Saito K, Iwata S, Miyagawa I, Seto Y, Momohara S, Nagasawa H, Kameda H, Kaneko Y, Izumi K, Amano K, Takeuchi T
  • Journal Title: Mod Rheumatol Volume: 22 Issue: 2 Pages: 186-94
  • DOI: 10.1007/s10165-011-0510-z
  • NAID: 10030614929
  • Peer Reviewed
• [Journal Article] Effectiveness and safety of adalimumab in Japanese patients with rheumatoid arthritis : Retrospective analyses of data collected during the first year of adalimumab treatment in routine clinical practice (HARMONY study) (2011)
  • Author(s): Takeuchi T, Tanaka Y, Kaneko Y, Kameda H, Amano K, Yamanaka H., et.al
  • Journal Title: Mod Rheum Volume: 6,Sep(Online) Issue: 3 Pages: 327-38
  • DOI: 10.1007/s10165-011-0516-6
  • NAID: 10030782043
  • Peer Reviewed
• [Journal Article] Clinical, radiographic and functional effectiveness of tocilizumab for rheumatoid arthritis patients-REACTION 52-week study (2011)
  • Author(s): Takeuchi T, Tanaka Y, Amano K, Hoshi D, Nawata M, Nagasawa H, Sato E, Saito K, Kaneko Y, Fukuyo S, Kurasawa T, Hanami K, Kameda H, Yamanaka H
  • Journal Title: Rheumatology(Oxford) Volume: 50 Issue: 10 Pages: 1908-15
  • DOI: 10.1093/rheumatology/ker221
  • Peer Reviewed
• [Journal Article] Sensitivity and specificity of 2010 rheumatoid arthritis classification criteria (2011)
  • Author(s): Kaneko Y, Kuwana M, Kameda H, Takeuchi T
  • Journal Title: Rheumatology(Oxford) Volume: 50 Issue: 7 Pages: 1268-74
  • DOI: 10.1093/rheumatology/keq442
  • Peer Reviewed
• [Presentation] Distinct arthropaties in patients with anti-aminoacyl tRNA synthetase antibodies : utility of autoantibody profiles in discrimination (2013)
  • Author(s): Yuko Kaneko, Hironari Hanaoka, Michito Hirakata, Tsutomu Takeuchi, Masataka Kuwana
  • Organizer: American College of Rheumatology 77th Annual Meeting
  • Place of Presentation: San Diego
• [Presentation] Adding tocilizumab or switching to tocilizumab monotherapy in RA patients with inadequate response to methotrexate : 24-week results from a randomized controlled study (SURPRISE study) (2013)
  • Author(s): Tsutomu. Takeuchi, Yuko Kaneko, Tatsuya Atsumi, Yoshiya Tanaka, M. Inoh, H. Kobayashi, Koichi Amano, M Miyata, Y Murakawa, Takao Fujii, Atushi Kawakami, Hisashi Yamanaka, Kazuhiko Yamamoto, Nobuyuki Miyasaka, Tsuneyo Mimori
  • Organizer: EULAR 2013-Annual European Congress on Rheumatology
  • Place of Presentation: Madrid, Spain
• [Presentation] 関節リウマチの治療 DMARDs・NSAIDs 初発関節リウマチ患者に対するメソトレキセート治療で血漿IL-6は低下し、治療後IL-6は関節破壊のバイオマーカーとなりうる． (2013)
  • Author(s): 仁科 直, 金子 祐子, 亀田 秀人, 桑名 正隆, 竹内 勤．
  • Organizer: 第57回リウマチ学会総会
  • Place of Presentation: 京都
• [Presentation] シンポジウム初期関節リウマチの診断と治療関節リウマチ新分類基準の検証 (2012)
  • Author(s): 金子祐子
  • Organizer: 日本画像医学会
  • Place of Presentation: 東京都
  • Year and Date: 2012-02-17
• [Presentation] 関節リウマチの治療DMARDs・NSAIDs初発関節リウマチ患者に対するメソトレキセート治療で血漿IL-6は低下し、治療後IL-6は関節破壊のバイオマーカーとなりうる (2012)
  • Author(s): 仁科直,金子祐子,亀田秀人,桑名正隆,竹内勤
  • Organizer: 第57回リウマチ学会総会
  • Place of Presentation: 京都
• [Presentation] How to Assess Risks for Pulmonary Infection in Patients Receiving Immunosuppressive Treatment for Rheumatic Diseases? A Report From a Large-Scale Prospective Cohort Study (2012)
  • Author(s): Hayato Yamazaki, Ryoko Sakai, Ryuji Koike, Yasunari Miyazaki, Michi Tanaka, Toshihiro Nanki, Kaori Watanabe, Shinsuke Yasuda, Takashi Kurita, Yuko Kaneko, Yoshiya Tanaka, Yasuhiko Nishioka, Yoshinari Takasaki, Kenji Nagasaka, Koichi Amano, Shigeto Tohma, Makoto Dohi, Takahiko Sugihara, Haruhito Sugiyama, Yasushi Kawaguchi, Naohiko Inase, Sae Ochi, Hiroyuki Hagiyama, Nobuyuki Miyasaka, Masayoshi Harigai
  • Organizer: American College of Rheumatology 76th Annual Meeting
  • Place of Presentation: Washington
• [Presentation] Lack of additive benefits of concomitant methotrexate use to tocilizumab monotherapy for rheumatoid arthritis in daily clinical practice (2012)
  • Author(s): Keisuke Izumi, Yuko Kaneko, Hidekata Yasuoka, Noriyuki Seta, Hideto Kameda, Masataka Kuwana, Tsutomu Takeuchi
  • Organizer: American College of Rheumatology 76th Annual Meeting
  • Place of Presentation: Washington
• [Presentation] A Single Nucleotide Polymorphism of Tumor Necrosis Factor Receptor-Associated Factor 1 Predicts Clinical Response to Anti-Tumor Necrosis Factor Treatments in Japanese Patients with Rheumatoid Arthritis (2012)
  • Author(s): Tetsuya Nishimoto, Noriyuki Seta, Ryusuke Anan, Tatsuya Yamamoto, Yuko Kaneko, Masataka Kuwana, Tsutomu Takeuchi
  • Organizer: American College of Rheumatology 76th Annual Meeting
  • Place of Presentation: Washington
• [Presentation] Interleukin-6 As a Biomarker for the Clinical and Radiological Effectiveness of Methotrexate in Rheumatoid Arthritis (2012)
  • Author(s): Naoshi Nishina, Hideto Kameda, Yuko Kaneko, Masataka Kuwana, Tsutomu Takeuchi
  • Organizer: American College of Rheumatology 76th Annual Meeting
  • Place of Presentation: Washington
• [Presentation] Fc Receptor IIIb Polymorphism Is Associated with Injection Reaction to Adalimumab in Patients with Rheumatoid Arthritis (2012)
  • Author(s): Masako Tsukamoto, Yosuke Hashimoto, Tatsuhiro Ohshige, Keiko Yoshimoto, Yuko Kaneko, Hideto Kameda, Tsutomu Takeuchi
  • Organizer: American College of Rheumatology 76th Annual Meeting
  • Place of Presentation: Washington
• [Presentation] Efficacy and safety of tocilizumab in patients with rheumatoid arthritis in the presence or absence or previous treatment with biologics and concomitant treatment with methotrexate (2012)
  • Author(s): Keisuke Izumi, Yuko Kaneko, Hidekata Yasuoka, Noriyuki Seta, Hideto Kameda, Masataka Kuwana, Tsutomu Takeuchi
  • Organizer: EULAR 2012-Annual European Congress on Rheumatology
  • Place of Presentation: Berlin, German
• [Presentation] TCZ観察研究前治療生物学的製剤およびMTX併用の有無で層別化した関節リウマチに対するトシリズマブの有用性の検討 (2012)
  • Author(s): 泉啓介,金子祐子,安岡秀剛,瀬田範行,亀田秀人,桑名正隆,竹内勤, 他
  • Organizer: 第56回リウマチ学会総会
  • Place of Presentation: 東京都
• [Presentation] バイオマーカー電気化学発光マルチサイトカインELISAを用いた関節リウマチ患者に対するアバタセプトの効果予測 (2012)
  • Author(s): 菊池潤,亀田秀人,吉本桂子,金子祐子,安岡秀剛,瀬田範行,桑名正隆,竹内勤, 他
  • Organizer: 第56回リウマチ学会総会
  • Place of Presentation: 東京都
• [Presentation] シンポジウム関節リウマチ寛解基準検証 : 慶應免疫統括センターにおける寛解 (2012)
  • Author(s): 金子祐子
  • Organizer: 第56回リウマチ学会総会
  • Place of Presentation: 東京都
• [Presentation] Interleukin-6 as a biomarker for the clinical and radiological effectiveness of methotrexate in rheumatoid arthritis (2012)
  • Author(s): 仁科直
  • Organizer: Amrican College of Rheumatology
  • Place of Presentation: Washington
• [Presentation] Discrepancy between patient and physician in assessment of global severity in early rheumatoid arthritis (2011)
  • Author(s): Yuko Kaneko, Masataka Kuwana, Tsutomu Takeuchi
  • Organizer: 1st Bio-Rheumatology International Congress (BRIC2011)
  • Place of Presentation: Makuhari, Japan
• [Presentation] (2011)
  • Author(s): Michi Tanaka, Yoshiya Tanaka, Makoto Doi, Yasushi Kawaguchi, Yoshinari Takasaki, Hideto Kameda, Shigeto Tohma, Yasuhiko Nishioka, Shinsuke Yasuda, Naohiko Inase, Yuko Kaneko, Ryoko Sakai, Toshihiro Nanki, Ryuji Koike, Kaori Watanabe, Hayato Yamazaki, Nobuyuki Miyasaka, Masayoshi Harigai
  • Organizer: 1st Symposium of the Asia Pacific League of Associations for Rheumatology(APLAR2011)
  • Place of Presentation: Taipei, Taiwan
• [Presentation] Single nucleotide polymorphism (SNP) within gene for the TNF receptor-associated factor 1 (TRAF1) predicts the clinical response to anti-TNF agents in Japanese patients with rheumatoid arthritis (2011)
  • Author(s): Tetsuya Nishimoto, Noriyuki Seta, Ryusuke Anan, Tatsuya Yamamoto, Yuko Kaneko, Masataka Kuwana, Tsutomu Takeuchi
  • Organizer: American College of Rheumatology 75th Annual Meeting
  • Place of Presentation: Chicago
• [Presentation] 関節リウマチ疾患活動性評価における患者-医師不一致に関する検討SAKURA study (2011)
  • Author(s): 金子祐子,桑名正隆,安岡秀剛,瀬田範行,亀田秀人,竹内勤
  • Organizer: 第55回リウマチ学会総会
  • Place of Presentation: 神戸市
• [Presentation] ACR/EULAR関節リウマチ分類基準の妥当性について国内5コホートを用いた2010ACR/EULAR RA新分類基準検証結果のまとめ (2011)
  • Author(s): 針谷正祥,金子祐子,川上純,當間重人,中島亜矢子
  • Organizer: 第55回リウマチ学会総会
  • Place of Presentation: 神戸市
• [Presentation] 関節リウマチの関節外病変関節リウマチ(RA)患者における動脈硬化の評価SAKURA study (2011)
  • Author(s): 井上有美子,金子祐子,安岡秀剛,瀬田範行,亀田秀人,桑名正隆,竹内勤
  • Organizer: 第55回リウマチ学会総会
  • Place of Presentation: 神戸市
• [Presentation] Evaluation of clinical, structural and functional remission in rheumatoid arthritis patients treated with tocilizumab in daily clinical practice -sub analysis of the Reaction study by disease duration- (2011)
  • Author(s): Tsutomu Takeuchi, Yoshiya Tanaka, Koichi Amano, Eichi Tanaka, Masao Nawata, Hayato Nagasawa, Daisuke Hoshi, Kazuyoshi Saito, Shunsuke Fukuyo, K Hanami, Hideto Kameda, Takahiko Kurasawa, Yuko Kaneko, Hisashi Yamanaka
  • Organizer: EULAR 2011-Annual European Congress on Rheumatology
  • Place of Presentation: London, United Kingdom
• [Presentation] TNF Inhibitors reduced structural changes to"ZERO"in patients with rheumatoid arthritis, as interium report of ZERO-J study (2011)
  • Author(s): Yoshiya Tanaka, Hisashi Yamanaka, Takao Koike, Nobuyuki Miyasaka, Tsuneyo Mimori, Tsutomu Takeuchi, Takayuki Sumida, Kazuhiko Yamamoto, Shintaro Hirata, Masao Nawata, Shunsuke Fukuyo, Eiichi Tanaka , Kosaku Murakami, Yuko Kaneko, Kazuyoshi Saito
  • Organizer: EULAR 2011-Annual European Congress on Rheumatology
  • Place of Presentation: London, United Kingdom
• [Book] 膠原病の肺合併症マニュア (2012)
  • Author(s): 金子祐子(宮坂信彦編)
  • Publisher: 医薬ジャーナル社
• [Book] 関節リウマチ治療実践バイブル (2012)
  • Author(s): 金子祐子
  • Publisher: 南江堂
• [Book] アレルギー・リウマチ膠原病診療ガイドライン (2012)
  • Author(s): 金子祐子,竹内勤
  • Publisher: 総合医学社