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文献精选 > 近年高分"阿尔茨海默病"研究（IF≥30，近5年）

Atopic dermatitis: an expanding therapeutic pipeline for a complex disease. ​

文献信息 ​

DOI10.1038/s41573-021-00266-6
PMID34417579
期刊Nature reviews. Drug discovery
影响因子101.8
JCR 分区Q1
发表年份2022
被引次数203
关键词特应性皮炎, 治疗策略, 靶向药物
文献类型Journal Article, Review
ISSN1474-1776
页码21-40
期号21(1)
作者Thomas Bieber

一句话小结 ​

本综述探讨了特应性皮炎（AD）的复杂病理机制及其治疗挑战，强调了新型治疗靶点和药物候选者的发现，尤其是已获批准的生物制剂和正在开发的化合物。研究指出，精准医学方法在AD的预防和长期控制中具有重要的潜力。

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特应性皮炎 · 治疗策略 · 靶向药物

摘要 ​

特应性皮炎（AD）是一种常见的慢性炎症性皮肤疾病，其复杂的病理生理机制导致了广泛的临床表型。由于现有疗法的有限效果，AD的治疗仍然具有挑战性。然而，近年来对疾病机制的理解进展促进了新型潜在治疗靶点和药物候选者的发现。除了在欧洲获得批准的IL-4Ra抑制剂dupilumab、抗IL-13抑制剂tralokinumab和JAK1/2抑制剂baricitinib外，目前还有超过70种新化合物正在开发中。本综述评估了目前针对AD的各种策略和新型药物，并强调了精准医学方法在预防和更有效地长期控制这一复杂疾病方面的潜力。

英文摘要 ​

Atopic dermatitis (AD) is a common chronic inflammatory skin disease with a complex pathophysiology that underlies a wide spectrum of clinical phenotypes. AD remains challenging to treat owing to the limited response to available therapies. However, recent advances in understanding of disease mechanisms have led to the discovery of novel potential therapeutic targets and drug candidates. In addition to regulatory approval for the IL-4Ra inhibitor dupilumab, the anti-IL-13 inhibitor tralokinumab and the JAK1/2 inhibitor baricitinib in Europe, there are now more than 70 new compounds in development. This Review assesses the various strategies and novel agents currently being investigated for AD and highlights the potential for a precision medicine approach to enable prevention and more effective long-term control of this complex disease.

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主要研究问题 ​

  1. 在治疗特应性皮炎方面，除了现有的生物制剂，还有哪些新兴的治疗方法正在研发中？
  2. 目前针对特应性皮炎的精准医疗策略具体包括哪些方面，如何提高患者的个体化治疗效果？
  3. 特应性皮炎的复杂病理机制如何影响不同患者对治疗的反应，是否有研究揭示了这一点？
  4. 在新药研发过程中，如何评估这些新化合物对特应性皮炎不同临床表型的有效性？
  5. 除了药物治疗，生活方式和环境因素在特应性皮炎管理中起到什么样的作用，是否有相关的研究支持？

核心洞察 ​

研究背景和目的 ​

特应性皮炎（Atopic Dermatitis, AD）是一种常见的慢性炎症性皮肤病，具有复杂的病理生理机制，表现出多种临床表型。AD的治疗一直具有挑战性，现有疗法的效果有限。近年来，对AD机制的深入理解促使新治疗靶点和药物候选者的发现。本文综述了目前正在研究的AD治疗策略和新药物，并强调了精准医学在预防和长期控制AD方面的潜力。

主要方法/材料/实验设计 ​

研究采用了系统性文献综述的方法，评估了AD的病理生理、临床表现及其治疗进展。以下是研究的技术路线图：

Mermaid diagram

关键结果和发现 ​

  1. AD的流行病学：约80%的AD病例在婴幼儿期发病，成年人的患病率较低。
  2. 临床表型：AD的表现因年龄、病情严重程度和种族背景而异，影响患者生活质量。
  3. 治疗进展：
    • 生物制剂：如IL-4Ra抑制剂dupilumab和IL-13抑制剂tralokinumab已获得批准。
    • JAK抑制剂：如baricitinib的临床试验显示出良好的疗效。
    • 微生物组调节：新的治疗策略包括微生物移植和细菌替代，初步结果显示改善皮肤状况。
    • 针对皮肤屏障功能：新药物正在开发以修复受损的皮肤屏障。

主要结论/意义/创新性 ​

本文指出，AD的复杂性要求治疗策略的多样化。精准医学的应用可能会改善AD的治疗效果，特别是在儿童和老年患者中。研究强调了个体化治疗的重要性，并提出了在AD管理中考虑表型和基因型差异的必要性。

研究局限性和未来方向 ​

  1. 局限性：目前对AD的理解仍不够全面，特别是在不同人群和亚型中的表现。
  2. 未来方向：
    • 需要进行更大规模的临床试验以验证新药物的有效性和安全性。
    • 加强对AD病理机制的研究，以开发更具针对性的治疗方法。
    • 建立长期患者登记和生物样本库，以支持未来的研究和精准医学应用。

总结 ​

特应性皮炎的治疗正在朝着个性化和精准化的方向发展，新的生物制剂和小分子药物正在不断进入临床试验阶段。未来的研究将致力于深入理解AD的复杂机制，以期实现更有效的治疗方案。

参考文献 ​

  1. NK-1 Antagonists and Itch. - Sonja Ständer;Thomas A Luger - Handbook of experimental pharmacology (2015)
  2. Lipid abnormalities in atopic skin are driven by type 2 cytokines. - Evgeny Berdyshev;Elena Goleva;Irina Bronova;Nathan Dyjack;Cydney Rios;John Jung;Patricia Taylor;Mingeum Jeong;Clifton F Hall;Brittany N Richers;Kathryn A Norquest;Tao Zheng;Max A Seibold;Donald Ym Leung - JCI insight (2018)
  3. Nociceptive signaling mediated by P2X3, P2X4 and P2X7 receptors. - Kazuhide Inoue;Makoto Tsuda - Biochemical pharmacology (2021)
  4. P2X3-Receptor Antagonists as Potential Antitussives: Summary of Current Clinical Trials in Chronic Cough. - Peter V Dicpinigaitis;Lorcan P McGarvey;Brendan J Canning - Lung (2020)
  5. A systematic review and meta-analysis of the regional and age-related differences in atopic dermatitis clinical characteristics. - Yik Weng Yew;Jacob P Thyssen;Jonathan I Silverberg - Journal of the American Academy of Dermatology (2019)
  6. A selective antagonist of histamine H₄ receptors prevents antigen-induced airway inflammation and bronchoconstriction in guinea pigs: involvement of lipocortin-1. - T Somma;L Cinci;G Formicola;A Pini;R Thurmond;M Ennis;D Bani;E Masini - British journal of pharmacology (2013)
  7. Therapeutic responses to Roseomonas mucosa in atopic dermatitis may involve lipid-mediated TNF-related epithelial repair. - Ian A Myles;Carlo R Castillo;Kent D Barbian;Kishore Kanakabandi;Kimmo Virtaneva;Emily Fitzmeyer;Monica Paneru;Francisco Otaizo-Carrasquero;Timothy G Myers;Tovah E Markowitz;Ian N Moore;Xue Liu;Marc Ferrer;Yosuke Sakamachi;Stavros Garantziotis;Muthulekha Swamydas;Michail S Lionakis;Erik D Anderson;Noah J Earland;Sundar Ganesan;Ashleigh A Sun;Jenna R E Bergerson;Robert A Silverman;Maureen Petersen;Craig A Martens;Sandip K Datta - Science translational medicine (2020)
  8. Impact of atopic dermatitis on quality of life in adults: a systematic review and meta-analysis. - Gurkiran Birdi;Richard Cooke;Rebecca C Knibb - International journal of dermatology (2020)
  9. Long-term safety and efficacy of delgocitinib ointment, a topical Janus kinase inhibitor, in adult patients with atopic dermatitis. - Hidemi Nakagawa;Osamu Nemoto;Atsuyuki Igarashi;Hidehisa Saeki;Ryusei Murata;Hironobu Kaino;Takeshi Nagata - The Journal of dermatology (2020)
  10. Pharmacological properties of JTE-052: a novel potent JAK inhibitor that suppresses various inflammatory responses in vitro and in vivo. - Atsuo Tanimoto;Yoshihiro Ogawa;Chika Oki;Yukari Kimoto;Keisuke Nozawa;Wataru Amano;Satoru Noji;Makoto Shiozaki;Akira Matsuo;Yuichi Shinozaki;Mutsuyoshi Matsushita - Inflammation research : official journal of the European Histamine Research Society ... [et al.] (2015)

引用本文的文献 ​

  1. [Inappropriate systemic therapy in severe atopic dermatitis-severe long-term damage]. - F Abeck;N Booken;S Schneider - Dermatologie (Heidelberg, Germany) (2022)
  2. The link between atopic dermatitis and asthma- immunological imbalance and beyond. - Martina Yaneva;Razvigor Darlenski - Asthma research and practice (2021)
  3. Flare management in atopic dermatitis: from definition to treatment. - Giampiero Girolomoni;Valentina Maria Busà - Therapeutic advances in chronic disease (2022)
  4. The Therapeutic Prospects of Targeting IL-1R1 for the Modulation of Neuroinflammation in Central Nervous System Disorders. - João P Luís;Carlos J V Simões;Rui M M Brito - International journal of molecular sciences (2022)
  5. Anti-atopic dermatitis effects of Parasenecio auriculatus via simultaneous inhibition of multiple inflammatory pathways. - Yujin Kwon;Su-Yeon Cho;Jaeyoung Kwon;Min Hwang;Hoseong Hwang;Yoon Jin Kang;Hyeon-Seong Lee;Jiyoon Kim;Won Kyu Kim - BMB reports (2022)
  6. Bruton's tyrosine kinase inhibition-An emerging therapeutic strategy in immune-mediated dermatological conditions. - Pedro Mendes-Bastos;Ana Brasileiro;Pavel Kolkhir;Stefan Frischbutter;Jörg Scheffel;Sherezade Moñino-Romero;Marcus Maurer - Allergy (2022)
  7. Atopic Dermatitis Pathogenesis: Lessons From Immunology. - Luis F Santamaria-Babí - Dermatology practical & conceptual (2022)
  8. 1-Iodohexadecane Alleviates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis in Mice: Possible Involvements of the Skin Barrier and Mast Cell SNARE Proteins. - Do Yoon Kim;Kyung-Jong Won;Dae Il Hwang;Nan Young Kim;Bokyung Kim;Hwan Myung Lee - Molecules (Basel, Switzerland) (2022)
  9. Multiple Roles for Cytokines in Atopic Dermatitis: From Pathogenic Mediators to Endotype-Specific Biomarkers to Therapeutic Targets. - Luca Fania;Gaia Moretta;Flaminia Antonelli;Enrico Scala;Damiano Abeni;Cristina Albanesi;Stefania Madonna - International journal of molecular sciences (2022)
  10. Immunopathology and Immunotherapy of Inflammatory Skin Diseases. - Ahreum Song;Sang Eun Lee;Jong Hoon Kim - Immune network (2022)

... (193 更多 篇文献)

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