Abstract：
UNASSIGNED: Asthma is a major global disease affecting adults and children, which can lead to hospitalization and death due to breathing difficulties. Although targeted monoclonal antibody therapies have revolutionized treatment of severe asthma, some patients still fail to respond. Here we critically evaluate the literature on biologic therapy failure in asthma patients with particular reference to anti-drug antibody production, and subsequent loss of response, as the potential primary cause of drug failure in asthma patients.
UNASSIGNED: Encouragingly, asthma in most cases responds to treatment, including the use of an increasing number of biologic drugs in moderate to severe disease. This includes monoclonal antibody inhibitors of immunoglobulin E and cytokines, including interleukin 4, 5, or 13 and thymic stromal lymphopoietin. These limit mast cell and eosinophil activity that cause the symptomatic small airways obstruction and exacerbations.
UNASSIGNED: Despite humanization of the antibodies, it is evident that benralizumab; dupilumab; mepolizumab; omalizumab; reslizumab and tezepelumab all induce anti-drug antibodies to some extent. These can contribute to adverse events including infusion reactions, serum sickness, anaphylaxis and potentially disease activity due to loss of therapeutic function. Monitoring anti-drug antibodies (ADA) may allow prediction of future treatment-failure in some individuals allowing treatment cessation and switching therefore potentially limiting disease breakthrough.
UNASSIGNED: Encouragingly, asthma in most cases responds to treatment, including the use of an increasing number of biologic drugs in moderate to severe disease. This includes monoclonal antibody inhibitors of immunoglobulin E and cytokines, including interleukin 4, 5, or 13 and thymic stromal lymphopoietin. These limit mast cell and eosinophil activity that cause the symptomatic small airways obstruction and exacerbations.
UNASSIGNED: Despite humanization of the antibodies, it is evident that benralizumab; dupilumab; mepolizumab; omalizumab; reslizumab and tezepelumab all induce anti-drug antibodies to some extent. These can contribute to adverse events including infusion reactions, serum sickness, anaphylaxis and potentially disease activity due to loss of therapeutic function. Monitoring anti-drug antibodies (ADA) may allow prediction of future treatment-failure in some individuals allowing treatment cessation and switching therefore potentially limiting disease breakthrough.
摘要：
哮喘是影响成人和儿童的主要全球性疾病，这可能会导致住院和因呼吸困难而死亡。尽管靶向单克隆抗体疗法彻底改变了严重哮喘的治疗方法，一些患者仍然没有反应。在这里，我们批判性地评估了哮喘患者生物治疗失败的文献，特别是抗药物抗体的产生，以及随后的反应丧失，作为哮喘患者药物失效的潜在主要原因。
■令人鼓舞的是，哮喘在大多数情况下对治疗有反应，包括在中度至重度疾病中使用越来越多的生物药物。这包括免疫球蛋白E和细胞因子的单克隆抗体抑制剂，包括白细胞介素4、5或13和胸腺基质淋巴细胞生成素。这些限制了肥大细胞和嗜酸性粒细胞的活动，导致有症状的小气道阻塞和恶化。
■尽管抗体人源化，很明显,贝那利珠单抗;dupilumab;美泊利单抗;奥马珠单抗;瑞利珠单抗和替齐单抗均在一定程度上诱导抗药物抗体.这些可能导致不良事件，包括输液反应，血清病,过敏反应和潜在的疾病活动由于丧失治疗功能。监测抗药物抗体(ADA)可以允许预测某些个体的未来治疗失败,从而允许治疗停止和转换,因此潜在地限制疾病突破。
■令人鼓舞的是，哮喘在大多数情况下对治疗有反应，包括在中度至重度疾病中使用越来越多的生物药物。这包括免疫球蛋白E和细胞因子的单克隆抗体抑制剂，包括白细胞介素4、5或13和胸腺基质淋巴细胞生成素。这些限制了肥大细胞和嗜酸性粒细胞的活动，导致有症状的小气道阻塞和恶化。
■尽管抗体人源化，很明显,贝那利珠单抗;dupilumab;美泊利单抗;奥马珠单抗;瑞利珠单抗和替齐单抗均在一定程度上诱导抗药物抗体.这些可能导致不良事件，包括输液反应，血清病,过敏反应和潜在的疾病活动由于丧失治疗功能。监测抗药物抗体(ADA)可以允许预测某些个体的未来治疗失败,从而允许治疗停止和转换,因此潜在地限制疾病突破。
