PDF(Pubmed)
Abstract：
Asthma is a heterogeneous inflammatory disease of the airways, affecting many children, adolescents, and adults worldwide. Up to 10% of people with asthma have severe disease, associated with a higher risk of hospitalizations, greater healthcare costs, and poorer outcomes. Patients with severe asthma generally require high-dose inhaled corticosteroids and additional controller medications to achieve disease control; however, many patients remain uncontrolled despite this intensive treatment. The treatment of severe uncontrolled asthma has improved with greater understanding of asthma pathways and phenotypes as well as the advent of targeted biologic therapies. Tezepelumab, a monoclonal antibody, blocks thymic stromal lymphopoietin, an epithelial cytokine that has multifaceted effects on the initiation and persistence of asthma inflammation and pathophysiology. Unlike other biologic treatments, tezepelumab has demonstrated efficacy across severe asthma phenotypes, with the magnitude of effects varying by phenotype. Here we describe the anti-inflammatory effects and efficacy of tezepelumab across the most relevant phenotypes of severe asthma. Across clinical studies, tezepelumab reduced annualized asthma exacerbation rates versus placebo by 63-71% in eosinophilic severe asthma, by 58-68% in allergic severe asthma, by 67-71% in allergic and eosinophilic severe asthma, by 34-49% in type 2-low asthma, and by 31-41% in oral corticosteroid-dependent asthma. Furthermore, in all these asthma phenotypes, tezepelumab demonstrated higher efficacy in reducing exacerbations requiring hospitalizations or emergency department visits versus placebo. In patients with severe uncontrolled asthma, who commonly have multiple drivers of inflammation and disease, tezepelumab may modulate airway inflammation more extensively, as other available biologics block only specific downstream components of the inflammatory cascade.
Asthma is characterized by an immune response leading to airway inflammation. People with severe asthma may react to different triggers and develop different types of airway inflammation. In patients with asthma, a protein called thymic stromal lymphopoietin (TSLP) plays an important role in the immune response that leads to the signs and symptoms of asthma. TSLP is released by the airway lining in response to different asthma triggers, driving an immune chain reaction, leading to airway narrowing and tightening, increased airway inflammation, worsening asthma symptoms, and asthma attack. Tezepelumab is a monoclonal antibody (a type of protein) that prevents TSLP from attaching to its receptor, thereby blocking its activity, reducing airway inflammation and asthma symptoms. Tezepelumab is an add-on medicine for the treatment of people aged 12 years or older with severe asthma that is not controlled with their current medicines. In this article, we discuss how tezepelumab may work in different types of asthma, for example allergic asthma, eosinophilic asthma, and T2-low asthma. We also describe how effective tezepelumab is in these different asthma types, through the reduction of asthma attacks and improvement in lung function, symptom control, and quality of life, leading to fewer emergency department visits and hospitalizations for asthma.
Asthma is characterized by an immune response leading to airway inflammation. People with severe asthma may react to different triggers and develop different types of airway inflammation. In patients with asthma, a protein called thymic stromal lymphopoietin (TSLP) plays an important role in the immune response that leads to the signs and symptoms of asthma. TSLP is released by the airway lining in response to different asthma triggers, driving an immune chain reaction, leading to airway narrowing and tightening, increased airway inflammation, worsening asthma symptoms, and asthma attack. Tezepelumab is a monoclonal antibody (a type of protein) that prevents TSLP from attaching to its receptor, thereby blocking its activity, reducing airway inflammation and asthma symptoms. Tezepelumab is an add-on medicine for the treatment of people aged 12 years or older with severe asthma that is not controlled with their current medicines. In this article, we discuss how tezepelumab may work in different types of asthma, for example allergic asthma, eosinophilic asthma, and T2-low asthma. We also describe how effective tezepelumab is in these different asthma types, through the reduction of asthma attacks and improvement in lung function, symptom control, and quality of life, leading to fewer emergency department visits and hospitalizations for asthma.
摘要：
哮喘是气道的异质性炎症性疾病，影响了许多孩子，青少年,全世界的成年人。高达10％的哮喘患者患有严重疾病，与更高的住院风险相关，更高的医疗保健成本，和较差的结果。严重哮喘患者通常需要大剂量吸入糖皮质激素和额外的控制药物来实现疾病控制;然而，尽管进行了这种强化治疗，但许多患者仍然不受控制。随着对哮喘途径和表型的更多了解以及靶向生物疗法的出现，严重不受控制的哮喘的治疗得到了改善。Tezepelumab,单克隆抗体，阻断胸腺基质淋巴细胞生成素，一种对哮喘炎症和病理生理学的开始和持续有多方面影响的上皮细胞因子。与其他生物治疗不同，tezepelumab已证明对严重哮喘表型有效，效应的大小因表型而异。在这里，我们描述了tezepelumab在严重哮喘的最相关表型中的抗炎作用和功效。在整个临床研究中，在嗜酸性粒细胞重度哮喘中，与安慰剂相比，tezepelumab可将年度哮喘加重率降低63-71％，58-68%的过敏性严重哮喘患者，在过敏性和嗜酸性粒细胞严重哮喘中占67-71％，2型低哮喘患者的比例为34-49%，口服皮质类固醇依赖性哮喘的发病率为31-41%。此外，在所有这些哮喘表型中，与安慰剂相比,tezepelumab在减少需要住院治疗或急诊就诊的急性加重方面表现出更高的疗效.在严重未控制的哮喘患者中，他们通常有多种炎症和疾病的驱动因素，tezepelumab可能更广泛地调节气道炎症，因为其他可用的生物制剂仅阻断炎症级联反应的特定下游成分.
哮喘的特征在于导致气道炎症的免疫应答。患有严重哮喘的人可能会对不同的诱因做出反应，并发展出不同类型的气道炎症。在哮喘患者中，一种称为胸腺基质淋巴细胞生成素（TSLP）的蛋白质在导致哮喘体征和症状的免疫反应中起着重要作用。TSLP由气道衬里释放，以响应不同的哮喘触发因素，驱动免疫连锁反应，导致气道变窄和收紧，增加气道炎症，哮喘症状恶化,哮喘发作。Tezepelumab是一种单克隆抗体（一种蛋白质），可防止TSLP附着在其受体上，从而阻止了它的活动，减少气道炎症和哮喘症状。Tezepelumab是一种附加药物，用于治疗12岁或以上的严重哮喘患者，目前的药物无法控制。在这篇文章中,我们讨论了tezepelumab如何在不同类型的哮喘中发挥作用，例如过敏性哮喘，嗜酸性粒细胞哮喘,和T2-低哮喘。我们还描述了tezepelumab在这些不同类型的哮喘中的有效性，通过减少哮喘发作和改善肺功能，症状控制,和生活质量，导致更少的急诊就诊和哮喘住院。
哮喘的特征在于导致气道炎症的免疫应答。患有严重哮喘的人可能会对不同的诱因做出反应，并发展出不同类型的气道炎症。在哮喘患者中，一种称为胸腺基质淋巴细胞生成素（TSLP）的蛋白质在导致哮喘体征和症状的免疫反应中起着重要作用。TSLP由气道衬里释放，以响应不同的哮喘触发因素，驱动免疫连锁反应，导致气道变窄和收紧，增加气道炎症，哮喘症状恶化,哮喘发作。Tezepelumab是一种单克隆抗体（一种蛋白质），可防止TSLP附着在其受体上，从而阻止了它的活动，减少气道炎症和哮喘症状。Tezepelumab是一种附加药物，用于治疗12岁或以上的严重哮喘患者，目前的药物无法控制。在这篇文章中,我们讨论了tezepelumab如何在不同类型的哮喘中发挥作用，例如过敏性哮喘，嗜酸性粒细胞哮喘,和T2-低哮喘。我们还描述了tezepelumab在这些不同类型的哮喘中的有效性，通过减少哮喘发作和改善肺功能，症状控制,和生活质量，导致更少的急诊就诊和哮喘住院。
