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Algorithm of molecular targeted therapy constructed from ultrasound, biomarker and signaling

Research Project

Project/Area Number 15K19576
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Collagenous pathology/Allergology
Research InstitutionNagasaki University

Principal Investigator

KAWASHIRI Shinya  長崎大学, 医歯薬学総合研究科(医学系), 講師 (20457576)

Research Collaborator HUIZING Tom W. J.  ライデン大学
KAWAKAMI Atsushi  長崎大学, 大学院医歯薬学総合研究科リウマチ・膠原病内科学分野
NAKAMURA Hideki  長崎大学, 病院リウマチ・膠原病内科
ICHINOSE Kunihiro  長崎大学, 病院リウマチ・膠原病内科
IWAMOTO Naoki  長崎大学, 大学院医歯薬学総合研究科リウマチ・膠原病内科学分野
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords関節リウマチ / 関節超音波 / 分子標的治療 / バイオマーカー / 自己抗体 / 分子標的治療薬
Outline of Final Research Achievements

This study is a translational study of molecular target therapy (TNF inhibitor, IL-6 inhibitor, T cell selective costimulatory modulator, JAK inhibitor) for rheumatoid arthritis (RA), linking data from the Kyushu area multicenter ultrasound prospective cohort study to basic research. This cohort study targeted patients with molecular target therapy, and 340 patients have been entered. Based on therapeutic response evaluation by clinical disease activity, ultrasound synovitis score, multiple blood biomarkers, and X-ray, we aimed at construction of an adaptation algorithm of molecular target therapy. The combination of clinical information and blood biomarkers levels at baseline suggested the possibility to predict objective therapeutic response by ultrasound.

Academic Significance and Societal Importance of the Research Achievements

本研究は世界的にも稀有な超音波評価を主軸とした多施設共同前向き研究を基盤とする。RA治療は分子標的治療薬の導入により目覚ましく進歩したが、その適切な使い分けが重要な課題となっている。本研究では臨床情報、臨床的疾患活動性、超音波滑膜炎スコア、多数の血液バイオマーカー、骨X線による多角的評価を統合することで薬剤別の治療反応性を予測できる可能性が示唆され、RA治療にプレシジョン・メディシンの実現へと繋がると考える。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (29 results)

All 2019 2018 2017 2016 2015 Other

All Int'l Joint Research (3 results) Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (21 results) (of which Int'l Joint Research: 3 results,  Invited: 6 results)

  • [Int'l Joint Research] ライデン大学(オランダ)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] ライデン大学(オランダ)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research]

    • Related Report
      2017 Research-status Report
  • [Journal Article] Combination of ultrasound power Doppler-verified synovitis and seropositivity accurately identifies patients with early-stage rheumatoid arthritis.2019

    • Author(s)
      Kawashiri SY, Fujikawa K, Nishino A, Takatani A, Shimizu T, Umeda M, Fukui S, Igawa T, Koga T, Iwamoto N, Ichinose K, Tamai M, Nakamura H, Origuchi T, Mizokami A, Maeda T, Kawakami A
    • Journal Title

      Int J Rheum Dis.

      Volume: Epub ahead of print Issue: 5 Pages: 1-10

    • DOI

      10.1111/1756-185x.13543

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ultrasonographic efficacy of biologic and targeted synthetic DMARDs therapy in RA from multicenter RA ultrasound prospective cohort in Japan2018

    • Author(s)
      Nishino Ayako、Kawashiri Shin-ya、Koga Tomohiro、Iwamoto Naoki、Ichinose Kunihiro、Tamai Mami、Nakamura Hideki、Origuchi Tomoki、Ueki Yukitaka、Yoshitama Tamami、Eiraku Nobutaka、Matsuoka Naoki、Okada Akitomo、Fujikawa Keita、Hamada Hiroaki、Tsuru Tomomi、Nagano Shuji、Arinobu Yojiro、Hidaka Toshihiko、Kawakami Atsushi
    • Journal Title

      Arthritis Care & Research

      Volume: 26 Issue: 12 Pages: 1719-1726

    • DOI

      10.1002/acr.23551

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ultrasound-detected bone erosion is a relapse risk factor after discontinuation of biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis whose ultrasound power Doppler synovitis activity and clinical disease activity are well controlled2017

    • Author(s)
      Kawashiri SY, Fujikawa K, Nishino A, Okada A, Aramaki T, Shimizu T, Umeda M, Fukui S, Suzuki T, Koga T, Iwamoto N, Ichinose K, Tamai M, Mizokami A, Nakamura H, Origuchi T, Ueki Y, Aoyagi K, Maeda T, Kawakami A
    • Journal Title

      Arthritis Research & Therapy

      Volume: 19 Issue: 1 Pages: 108-108

    • DOI

      10.1186/s13075-017-1320-2

    • NAID

      120006987478

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Assessment of both articular synovitis and tenosynovitis by ultrasound is useful for evaluations of hand dysfunction in early rheumatoid arthritis patients2017

    • Author(s)
      Nishino A, Kawashiri SY, Shimizu T, Umeda M, Fukui S, Koga T, Iwamoto N, Ichinose K, Tamai M, Nakamura H, Origuchi T, Nagata Y, Maeda T, Aoyagi K, Kawakami A
    • Journal Title

      Modern Rheumatology

      Volume: 27 Issue: 4 Pages: 605-608

    • DOI

      10.1080/14397595.2016.1253813

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ultrasound disease activity of bilateral wrist and finger joints at three months reflects the clinical response at six months of patients with rheumatoid arthritis treated with biologic disease-modifying anti-rheumatic drugs.2017

    • Author(s)
      Kawashiri SY, Nishino A, Shimizu T, Umeda M, Fukui S, Nakashima Y, Suzuki T, Koga T, Iwamoto N, Ichinose K, Tamai M, Nakamura H, Origuchi T, Aoyagi K, Kawakami A.
    • Journal Title

      Modern Rheumatology

      Volume: 27 Issue: 2 Pages: 252-256

    • DOI

      10.1080/14397595.2016.1221874

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 「関節リウマチの診断と治療に関節エコー・MRIは必要か?」MRI・関節エコーによるRAの早期診断と治療反応の評価2018

    • Author(s)
      川尻真也、西野文子、高谷亜由子、玉井慎美、上谷雅孝、川上純
    • Organizer
      第62回日本リウマチ学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Combination of ultrasound power Doppler-verified synovitis and seropositivity accurately identifies patients with early rheumatoid arthritis2018

    • Author(s)
      Shin-ya Kawashiri, Keita Fujikawa, Ayako Nishino, Ayuko Takatani, Toshimasa Shimizu, Masataka Umeda, Shoichi Fukui, Takeshi Igawa, Tomohiro Koga, Naoki Iwamoto, Kunihiro Ichinose, Mami Tamai, Hideki Nakamura, Tomoki Origuchi, Akinari Mizokami, Atsushi Kawakami,
    • Organizer
      American college of Rheumatology Annual Meeting 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 「生物学的免疫治療のタイミングと使い分け:各領域の相違点から学ぶ」関節リウマチについて2018

    • Author(s)
      川尻真也
    • Organizer
      第46回臨床免疫学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 早期関節リウマチ患者における診断1年後の予後を規定するベースラインの因子2018

    • Author(s)
      川尻真也、清水俊匡、遠藤友志郎、岡本百々子、辻創介、高谷亜由子、住吉玲美、古賀智裕、井川敬、岩本直樹、一瀬邦弘、玉井慎美、中村英樹、折口智樹、川上純
    • Organizer
      第56回九州リウマチ学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 関節リウマチにおける寛解を目指した関節超音波の活用2018

    • Author(s)
      川尻真也、西野文子、川上純、吉玉珠美、榮樂信隆、松岡直樹、植木幸孝、岡田覚丈、都留智巳、日髙利彦、濱田浩朗、藤川敬太、永野修司、有信洋二郎、多田芳史
    • Organizer
      第55回九州リウマチ学会
    • Related Report
      2017 Research-status Report
  • [Presentation] アバタセプト治療関節リウマチ患者における骨関連バイオマーカーの評価:九州地区多施設共同RA超音波前方視的コホート研究.2017

    • Author(s)
      川尻真也,西野文子,植木幸孝,榮樂信隆,吉玉珠美,岡田覚丈,松岡直樹,藤川敬太,有信洋二郎,濱田浩朗,日髙利彦,永野修司,都留智巳,多田芳史,前田隆浩,川上純
    • Organizer
      第61回日本リウマチ学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] バイオマーカーと超音波指標で解析する関節リウマチにおける生物学的製剤治療の有効性の評価:九州地区多施設共同RA超音波コホート研究.2017

    • Author(s)
      川尻真也,西野文子,植木幸孝,榮樂信隆,吉玉珠美,岡田覚丈,松岡直樹,藤川敬太,有信洋二郎,濱田浩朗,日髙利彦,永野修司,都留智巳,多田芳史,前田隆浩,川上純
    • Organizer
      第61回日本リウマチ学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 関節エコーで診断確定した早期関節リウマチの特徴2017

    • Author(s)
      川尻真也,藤川敬太,西野文子,溝上明成,中村英樹,折口智樹,川上純
    • Organizer
      第54回九州リウマチ学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 関節リウマチ治療のエビデンスと経験から2017

    • Author(s)
      川尻真也,川上純
    • Organizer
      第45回日本臨床免疫学会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 関節リウマチの病態解析:超音波とバイオマーカー2017

    • Author(s)
      川尻真也,川上純
    • Organizer
      第32回日本臨床リウマチ学会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] バイオマーカーと超音波指標で解析する関節リウマチにおける生物学的製剤治療の有効性の評価:九州地区多施設共同RA超音波コホート研究2017

    • Author(s)
      川尻 真也、西野 文子、植木 幸孝、榮樂 信隆、吉玉 珠美、岡田 覚丈、松岡 直樹、藤川 敬太、前田 隆浩、川上 純
    • Organizer
      第114回日本内科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Evaluation of ultrasound-detecting efficacy of abatacept by profiling multiple serum cytokines, chemokines and bone-related biomarkers in rheumatoid arthritis patients: Kyushu multicenter rheumatoid arthritis ultrasound prospective observational cohort study2017

    • Author(s)
      Shin-ya Kawashiri, Ayako Nishino, Nobutaka Eiraku, Tamami Yoshitama, Naoki Matsuoka, Toshiyuki Aramaki, Yukitaka Ueki, Akitomo Okada, Hiroaki Hamada, Shuji Nagano, Keita Fujikawa, Atsushi Kawakami,
    • Organizer
      American college of Rheumatology Annual Meeting 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Power Dopper ultrasonography detects superior efficacy of non-TNF biologics compared to cycling of TNF inhibitors in RA patients inadequate response to first TNF inhibitors2017

    • Author(s)
      Ayako Nishino, Shin-ya Kawashiri, Nobutaka Eiraku, Tamami Yoshitama, Naoki Matsuoka, Toshiyuki Aramaki, Yukitaka Ueki, Akitomo Okada, Hiroaki Hamada, Shuji Nagano, Keita Fujikawa, Atsushi Kawakami,
    • Organizer
      American college of Rheumatology Annual Meeting 2017
    • Related Report
      2017 Research-status Report
  • [Presentation] 関節超音波を用いた分子標的治療薬の治療反応性の評価:九州地区多施設共同RA超音波前向きコホート研究2016

    • Author(s)
      西野文子、川尻真也、川上純、吉玉珠美、榮樂信隆、松岡直樹、植木幸孝、岡田覚丈、都留智巳、日髙利彦、濱田浩朗、藤川敬太、永野修司、有信洋二郎、多田芳文
    • Organizer
      第52回九州リウマチ学会
    • Place of Presentation
      熊本市民会館(熊本県・熊本市)
    • Year and Date
      2016-09-03
    • Related Report
      2016 Research-status Report
  • [Presentation] 今後のRA治療;Post RemissionイメージングによるRA治療選択の可能性2016

    • Author(s)
      川尻真也、青柳潔、川上純
    • Organizer
      第60回日本リウマチ学会総会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-04-21
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Ultrasound evaluation of the efficacy of biologic and targeted synthetic DMARDs toward rheumatoid arthritis patients: Kyushu multicenter rheumatoid arthritis ultrasound prospective observational cohort in Japan2016

    • Author(s)
      Ayako Nishino, Shin-ya Kawashiri, Atsushi Kawakami, Tamami Yoshitama, Nobutaka Eiraku, Naoki Matsuoka, Yukitaka Ueki, Akitomo Okada, Hiroaki Hamada, Toshihiko Hidaka, Shuji Nagano, Tomomi Tsuru, Keita Fujikawa, Yojiro Arinobu
    • Organizer
      第60回日本リウマチ学会総会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-04-21
    • Related Report
      2016 Research-status Report 2015 Research-status Report
  • [Presentation] 寛解後の減量・中止における関節エコーの意義2016

    • Author(s)
      川尻真也、青柳潔、川上純
    • Organizer
      第60回日本リウマチ学会総会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-04-21
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 関節超音波を用いた分子標的治療薬の治療反応性の評価: 九州地区多施設共同RA超音波前方視的コホート研究2016

    • Author(s)
      西野文子、川尻真也、川上純、吉玉珠美、榮樂信隆、松岡直樹、植木幸孝、岡田覚丈、 濱田浩朗、日髙利彦、 藤川敬太、 永野修司、都留智巳、有信洋二郎、田中良哉、井田弘明、 福田孝昭、金崎克也、大坪秀雄、泉原智麿、右田清志
    • Organizer
      第51回九州リウマチ学会
    • Place of Presentation
      宮崎市民プラザ(宮崎県・宮崎市)
    • Year and Date
      2016-03-05
    • Related Report
      2015 Research-status Report
  • [Presentation] Ultrasound evaluation of the efficacy of biologic and targeted synthetic DMARDs toward rheumatoid arthritis patients: Kyushu multicenter rheumatoid arthritis ultrasound prospective observational cohort in Japan2015

    • Author(s)
      Ayako Nishino, Shin-ya Kawashiri, Atsushi Kawakami, Tamami Yoshitama, Nobutaka Eiraku, Naoki Matsuoka, Yukitaka Ueki, Akitomo Okada, Hiroaki Hamada, Toshihiko Hidaka, Shuji Nagano, Tomomi Tsuru, Keita Fujikawa, Yojiro Arinobu
    • Organizer
      2015 American College of Rheumatology Annual Meeting
    • Place of Presentation
      アメリカ合衆国サンフランシスコ
    • Year and Date
      2015-11-07
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 関節超音波を用いた生物学的製剤の治療反応性の評価:生物学的製剤のスイッチングの観点から2015

    • Author(s)
      西野文子、川尻真也、川上純、吉玉珠美、榮樂信隆、松岡直樹、植木幸孝、岡田覚丈、 濱田浩朗、日髙利彦、 藤川敬太、 永野修司、都留智巳、有信洋二郎、田中良哉、井田弘明、 福田孝昭、金崎克也、大坪秀雄、泉原智麿、右田清志
    • Organizer
      第50回九州リウマチ学会
    • Place of Presentation
      鹿児島県医師会館(鹿児島県・鹿児島市)
    • Year and Date
      2015-09-05
    • Related Report
      2015 Research-status Report
  • [Presentation] 分子標的治療薬の治療早期における関節超音波検査の意義;九州地区多施設共同前向きRA超音波コホート研究2015

    • Author(s)
      西野文子、川尻真也、川上純、吉玉珠美、榮樂信隆、松岡直樹、植木幸孝、岡田覚丈、 濱田浩朗、日髙利彦、 藤川敬太、 永野修司、都留智巳、有信洋二郎、田中良哉、井田弘明、 福田孝昭、金崎克也、大坪秀雄、泉原智麿、右田清志
    • Organizer
      第59回日本リウマチ学会総会
    • Place of Presentation
      名古屋国際会議場(愛知県・名古屋市)
    • Year and Date
      2015-04-23
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2020-03-30  

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