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新型哮喘治疗方法:超越已获批的新型哮喘逐步升级疗法

Novel asthma treatments: Advancing beyond approved novel step-up therapies for asthma.

作者信息

Seluk Lior, Davis Andrea E, Rhoads Sarah, Wechsler Michael E

机构信息

Division of Pulmonary, Critical Care, and Sleep Medicine, National Jewish Health, Denver, Colorado.

Division of Pulmonary, Critical Care, and Sleep Medicine, National Jewish Health, Denver, Colorado; Division of Pulmonary Sciences and Critical Care Medicine, The Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado.

出版信息

Ann Allergy Asthma Immunol. 2025 Jan;134(1):9-18. doi: 10.1016/j.anai.2024.09.016. Epub 2024 Oct 10.

Abstract

Over the past 2 decades, the management of severe asthma has shifted from relying on inhaled corticosteroids and bronchodilators to more precise, targeted approaches. Monoclonal antibodies designed to address specific molecular pathways in asthma have transformed care for patients with severe asthma. Because therapy targeting IgE became the first biologic developed for allergic asthma in 2003, monoclonal antibodies targeting interleukin (IL)-5, IL-5 receptor, IL-4/-13 receptor, and thymic stromal lymphopoietin have been approved for treating difficult-to-treat asthma, improving symptoms, reducing exacerbations, and reducing oral corticosteroid dosing. Despite these advances, many patients continue to experience asthma exacerbations and symptoms and fail to achieve remission. To address this, pharmaceutical companies and researchers are exploring novel therapies targeting different aspects of asthma pathophysiology, including cytokines, enzymes, and cellular pathways. Innovative treatments such as inhaled biologics, ultra-long-acting biologics, and combination biologics are in development. New molecular targets, such as Bruton tyrosine kinase, OX-40 ligand, and Janus kinase, offer promise for addressing unmet needs in asthma care. Although many therapies have failed to get approval for use because of a lack of efficacy, trial design, or toxicity, these experiments still provide insights into asthma's underlying mechanisms. The future of asthma management looks promising, with emerging therapies aiming to improve patient outcomes. The challenge will lie in identifying the right therapy for each patient and developing personalized treatment strategies.

摘要

在过去20年中,重度哮喘的管理已从依赖吸入性糖皮质激素和支气管扩张剂转向更精确、有针对性的方法。旨在解决哮喘中特定分子途径的单克隆抗体改变了重度哮喘患者的治疗方式。由于针对IgE的疗法在2003年成为首个用于过敏性哮喘的生物制剂,针对白细胞介素(IL)-5、IL-5受体、IL-4/-13受体和胸腺基质淋巴细胞生成素的单克隆抗体已被批准用于治疗难治性哮喘,改善症状、减少发作并减少口服糖皮质激素的用量。尽管取得了这些进展,但许多患者仍继续经历哮喘发作和症状,且无法实现缓解。为解决这一问题,制药公司和研究人员正在探索针对哮喘病理生理学不同方面的新型疗法,包括细胞因子、酶和细胞途径。吸入性生物制剂、超长作用生物制剂和联合生物制剂等创新疗法正在研发中。诸如布鲁顿酪氨酸激酶、OX-40配体和Janus激酶等新的分子靶点为满足哮喘治疗中未满足的需求带来了希望。尽管许多疗法由于缺乏疗效、试验设计或毒性而未能获批使用,但这些实验仍为哮喘的潜在机制提供了见解。哮喘管理的未来看起来很有希望,新出现的疗法旨在改善患者的治疗效果。挑战将在于为每位患者确定正确的疗法并制定个性化的治疗策略。

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