Effective treatment of inflammatory diseases is often challenging owing to their heterogeneous pathophysiology. Understanding of the underlying disease mechanisms is improving and it is now clear that eosinophils play a complex pathophysiological role in a broad range of type 2 inflammatory diseases. Standard of care for these conditions often still includes oral corticosteroids (OCS) and/or cytotoxic immune therapies, which are associated with debilitating side effects. Selective, biological eosinophil-reducing agents provide treatment options that improve clinical symptoms associated with eosinophilic inflammation and reduce OCS use. Mepolizumab is a humanized monoclonal antibody that binds to and neutralizes interleukin-5, the major cytokine involved in eosinophil proliferation, activation, and survival. Mepolizumab is approved for the treatment of severe eosinophilic asthma, eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome. Additionally, the efficacy of add-on mepolizumab has been observed in patients with severe chronic rhinosinusitis with nasal polyposis and chronic obstructive pulmonary disease with an eosinophilic phenotype. Here, we review the development, approval, and real-world effectiveness of mepolizumab for the treatment of patients with severe eosinophilic asthma, from the DREAM to REALITI-A studies, and describe how knowledge from this journey extended to the use of mepolizumab and other biologics across a broad spectrum of eosinophilic diseases.

中文翻译：

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从 DREAM 到 REALITI-A 及超越：用于治疗嗜酸性粒细胞驱动疾病的美泊利单抗

炎症性疾病的有效治疗往往具有挑战性，因为它们的病理生理学存在异质性。对潜在疾病机制的了解正在提高，现在很清楚，嗜酸性粒细胞在广泛的 2 型炎症性疾病中发挥着复杂的病理生理学作用。这些病症的护理标准通常仍包括口服皮质类固醇 (OCS) 和/或细胞毒性免疫疗法，这些疗法与使人衰弱的副作用有关。选择性的生物嗜酸性粒细胞减少剂提供了改善与嗜酸性粒细胞炎症相关的临床症状并减少 OCS 使用的治疗选择。Mepolizumab 是一种人源化单克隆抗体，可结合并中和白细胞介素 5，白细胞介素 5 是参与嗜酸性粒细胞增殖、活化和存活的主要细胞因子。Mepolizumab被批准用于治疗严重的嗜酸性哮喘、嗜酸性肉芽肿伴多血管炎和嗜酸性粒细胞增多综合征。此外，在患有严重慢性鼻窦炎伴鼻息肉病和慢性阻塞性肺病伴嗜酸性粒细胞表型的患者中观察到附加美泊利单抗的疗效。在这里，我们回顾了从 DREAM 到 REALITI-A 研究的美泊利单抗治疗严重嗜酸性粒细胞性哮喘患者的开发、批准和实际有效性，并描述了从这一旅程中获得的知识如何扩展到美泊利单抗和其他药物的使用。涵盖广泛的嗜酸性粒细胞疾病的生物制剂。在患有严重慢性鼻窦炎伴鼻息肉和慢性阻塞性肺病伴嗜酸性粒细胞表型的患者中观察到附加美泊利单抗的疗效。在这里，我们回顾了从 DREAM 到 REALITI-A 研究的美泊利单抗治疗严重嗜酸性粒细胞性哮喘患者的开发、批准和实际有效性，并描述了从这一旅程中获得的知识如何扩展到美泊利单抗和其他药物的使用。涵盖广泛的嗜酸性粒细胞疾病的生物制剂。在患有严重慢性鼻窦炎伴鼻息肉和慢性阻塞性肺病伴嗜酸性粒细胞表型的患者中观察到附加美泊利单抗的疗效。在这里，我们回顾了从 DREAM 到 REALITI-A 研究的美泊利单抗治疗严重嗜酸性粒细胞性哮喘患者的开发、批准和实际有效性，并描述了从这一旅程中获得的知识如何扩展到美泊利单抗和其他药物的使用。涵盖广泛的嗜酸性粒细胞疾病的生物制剂。