アブストラクト
Japanese
| Title | 抗IL-6受容体抗体 (トシリズマブ) |
|---|---|
| Subtitle | 解説 : 免疫アレルギー疾患における分子標的薬 |
| Authors | 野澤智 |
| Authors (kana) | |
| Organization | 横浜市立大学大学院医学研究科発生成育小児医療学 |
| Journal | 日本小児アレルギー学会誌 |
| Volume | 38 |
| Number | 2 |
| Page | 204-210 |
| Year/Month | 2024 / |
| Article | 報告 |
| Publisher | 日本小児アレルギー学会 |
| Abstract | 「抄録」:トシリズマブ(tocilizumab, TCZ)は, わが国で初めて開発された抗interleukin(IL)-6受容体モノクローナル抗体である. TCZは可溶型または細胞膜結合型のIL-6受容体に結合し, IL-6とその受容体との結合を阻害することで, その後のシグナル伝達を抑制し炎症を沈静化する作用を有する. IL-6をターゲットにした薬剤は, TCZの他に数種類あるが, 小児ではTCZのみ保険適用となっている. 現在, TCZは若年性特発性関節炎や高安動脈炎などリウマチ性疾患に対し使用されているが, さらに, 近年, 腫瘍特異的T細胞輸注療法に伴うサイトカイン放出症候群, SARS-CoV-2による肺炎に対しても適用承認され, リウマチ分野以外にも用いられる薬剤である. 本稿では, TCZの作用機序, 適用, 導入前の評価, 副作用, 今後の展望について解説する. 主に小児科領域の臨床現場において, 適切な使用の参考として役立つことを期待する. |
| Practice | 臨床医学：内科系 |
| Keywords | IL-6, 若年性特発性関節炎, 小児リウマチ性疾患, 高安動脈炎, トシリズマブ, juvenile idiopathic arthritis, pediatric rheumatic diseases, Takayasu arteritis, tocilizumab |
English
| Title | Anti-Interleukin-6 receptor antibody |
|---|---|
| Subtitle | |
| Authors | Tomo Nozawa |
| Authors (kana) | |
| Organization | Department of Pediatrics, Graduate School of Medicine, Yokohama City University |
| Journal | The Japanese Journal of Pediatric Allergy and Clinical Immunology |
| Volume | 38 |
| Number | 2 |
| Page | 204-210 |
| Year/Month | 2024 / |
| Article | Report |
| Publisher | Japanese Society of Pediatric Allergy and Clinical Immunology |
| Abstract | [Summary]: Tocilizumab is the first anti-interleukin (IL)-6 receptor monoclonal antibody developed in Japan. Tocilizumab binds to the soluble or membrane-bound form of the IL-6 receptor to inhibit the binding of IL-6 to its receptor, which suppresses subsequent signaling and reduces IL-6-related systemic inflammation. Tocilizumab is currently used to treat rheumatic diseases such as juvenile idiopathic arthritis and Takayasu arteritis. Furthermore, tocilizumab was recently approved to treat cytokine release syndrome induced by tumor-specific T-cell infusion therapy and pneumonia caused by SARS-CoV-2, in addition to various rheumatic diseases. This study describes the mechanism of action, application, pre-introduction evaluation, side effects, and prospects of tocilizumab. This will provide useful guidance for its appropriate use in clinical practice. |
| Practice | Clinical internal medicine |
| Keywords | IL-6, juvenile idiopathic arthritis, pediatric rheumatic diseases, Takayasu arteritis, tocilizumab |
- 全文ダウンロード： 従量制、基本料金制の方共に770円(税込) です。
参考文献
- 1) Mihara M, et al. IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci(Lond) 2012 ; 122 : 143-159.
- 2) Hunter CA, Jones SA. IL-6 as a keystone cytokinein health and disease. Nat Immunol 2015 ; 16 : 448-457.
- 3) Narazaki M, Tanaka T, Kishimoto T. The role and therapeutic targeting of IL-6 in rheumatoidarthritis. Expert Rev Clin Immunol 2017 ; 13 : 535-551.
- 4) Ting EY, Yang AC, Tsai SJ. Role of Interleukin-6 in Depressive Disorder. Int J Mol Sci 2020 ; 21 : 2194.
- 5) Suematsu S, et al. Generation of plasmacytomas with the chromosomal translocation t(12 ; 15)in interleukin 6 transgenic mice. Proc Natl Acad Sci USA 1992 ; 89 : 232-235.
残りの29件を表示する
- 6) Katsume A, et al. Anti-interleukin 6(IL-6) recep-tor antibody suppresses Castleman's disease like symptoms emerged in IL-6 transgenic mice. Cy-tokine 2002 ; 20 : 304-311.
- 7) Holland SM, et al. STAT3 mutations in the hyper-IgE syndrome. N Engl J Med 2007 ; 357 : 1608-1619.
- 8) Kreins AY, et al. Human TYK2 deficiency : Myco-bacterial and viral infections without hyper-IgE syndrome. J Exp Med 2015 ; 212 : 1641-1662.
- 9) Schwerd T, et al. A biallelic mutation in IL6ST encoding the GP130 co-receptor causes immu-nodeficiency and craniosynostosis. J Exp Med 2017 ; 214 : 2547-2562.
- 10) Shahin T, et al. Selective loss of function variants in IL 6ST cause Hyper-IgE syndrome with dis-tinct impairments of T-cell phenotype and func-tion. Haematologica 2019 ; 104 : 609-621.
- 11) Chen YH, et al. Absence of GP130 cytokine recep-tor signaling causes extended Stuve-Wiedemann syndrome. J Exp Med 2020 ; 217 : e20191306.
- 12) Spencer S. Loss of the interleukin-6 receptor causes immunodeficiency, atopy, and abnormal inflammatory responses. J Exp Med 2019 ; 216 : 1986-1998.
- 13) Choy EH, et al. Translating IL-6 biology into ef-fective treatments. Nat Rev Rheumatol 2020 ; 16 : 335-345.
- 14) Jenkins RH, et al. Unravelling the broader com-plexity of IL-6 involvement in health and disease. Cytokine 2021 ; 148 : 155684.
- 15) Kistner TM, Pedersen BK, Lieberman DE. Inter-leukin 6 as an energy allocator in muscle tissue. Nat Metab 2022 ; 4 : 170-179.
- 16) Yokota S, et al. Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idi-opathic arthritis : a randomised, double-blind, placebo-controlled, withdrawal phase III trial. Lancet 2008 ; 371 : 998-1006.
- 17) De Benedetti F, et al. Randomized trial of tocilizu-mab in systemic juvenile idiopathic arthritis. N Engl J Med 2012 ; 367 : 2385-2395.
- 18) Yokota S. Longterm safety and effectiveness of the anti-interleukin 6 receptor monoclonal anti-body tocilizumab in patients with systemic juve-nile idiopathic arthritis in Japan. J Rheumatol 2014 ; 41 : 759-767.
- 19) 中外製薬株式会社. アクテムラ(R)点滴静注用 80mg, 200mg, 400mg全例調査 最終報告「関節リウマチ」「多関節に活動性を有する若年性特発性関節炎」. 2019. https://Chugai-pharm.jp/content/dam/chugai/product/act/div/survey/doc/20130723_act_epmpv_safe_ra.pdf
- 20) Nakaoka Y, et al. Efficacy and safety of tocilizu-mab in patients with refractory Takayasu arteri-tis : results from a randomised, double-blind, placebo-controlled, phase 3 trial in Japan(theTAKT study). Ann Rheum Dis 2018 ; 77 : 348-354.
- 21) 伊藤秀一, 森 雅亮監. 小児リウマチ疾患 トシリズマブ治療の理論と実際. メディカルレビュー社, 2023 : 32-38.
- 22) 厚生労働科学研究費補助金 難治性疾患等政策研究事業 小児期および成人移行期小児リウマチ患者の全国調査データの解析と両者の異同性に基づいた全国的「シームレス」診療ネットワーク構築による標準的治療の均てん化研究班 若年性特発関節炎分担班編. 若年性特発性関節炎における生物学的製剤使用の手引き 2020年版. 羊土社, 2020 : 26-32.
- 23) 日本肝臓学会 肝炎診療ガイドライン作成委員会(編). B型肝炎治療ガイドライン. 2017. https://www.jsh.or.jp/lib/files/medical/guidelines/jsh_guidlines/B_document-3_v2.pdf
- 24) 中外製薬株式会社. アクテムラ(R)点滴静注用80mg, 200mg, 400mg添付文書2023年9月改訂. https://chugai-harm.jp/content/dam/chugai/product/act/div/pi/doc/act_pi.pdf
- 25) 中外製薬株式会社. アクテムラ(R)皮下注162mg シリンジ, オートインジェクター 添付文書 2023年4月改訂. https://chugai-pharm.jp/content/dam/chugai/product/act/sc/pi/doc/act_sc_pi.pdf
- 26) Burmester GR, et al. Low immunogenicity of tocilizumab in patients with rheumatoid arthritis. Ann Rheum Dis 2017 ; 76 : 1078-1085.
- 27) Rocchi V, et al. Hypersensitivity reactions to to-cilizumab : role of skin tests in diagnosis. Rheuma-tology(Oxford) 2014 ; 53 : 1527-1529.
- 28) Galvao VR, et al. Hypersensitivity to biological agents-updated diagnosis, management, and treatment. J Allergy Clin Immunol Pract 2015 ; 3 : 175-185.
- 29) Yoshiki R, Nakamura M, Tokura Y. Drug erup-tion induced by IL-6 receptor inhibitor tocilizu-mab. J Eur Acad Dermatol Venereol 2010 ; 24 : 495-496.
- 30) Hayakawa M, et al. Tocilizumab-induced psoriasis-like eruption resolved by shortening the dose interval in a patient with rheumatoid arthri-tis : a case-based review. Rheumatol Int 2019 ; 39 : 161-166.
- 31) Strangfeld A, et al. Risk for lower intestinal perfo-rations in patients with rheumatoid arthritis treated with tocilizumab in comparison to treat-ment with other biologic or conventional syn-thetic DMARDs. Ann Rheum Dis 2017 ; 76 : 504-510.
- 32) Karin M, Clevers H. Reparative inflammation takes charge of tissue regeneration. Nature 2016 ; 529 : 307-315.
- 33) 厚生労働科学研究費補助金 難治性疾患等政策研究事業(難治性疾患政策研究事業) : 若年性特発性関節炎を主とした小児リウマチ性疾患の診断基準・重症度分類の標準化とエビデンスに基づいたガイドラインの策定に関する研究. 平成27年度総括・分担研究報告. 2015.
- 34) Khanna D. Tocilizumab in systemic sclerosis : a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med 2020 ; 8 : 963-974.
