Guy's Severe Asthma Centre, Guy's and St Thomas' NHS Trust, London, UK.
School of Immunology & Microbial Sciences, King's College London, London, UK.
Allergy. 2024 Nov;79(11):2943-2952. doi: 10.1111/all.16346. Epub 2024 Oct 12.
Eosinophilic asthma is characterized by frequent exacerbations, poor symptom control and accelerated lung function decline. It is now recognized that the immune response underlying eosinophilic asthma involves a complex network of interconnected pathways from both the adaptive and innate immune systems. Within this response, interleukin-5 (IL-5) plays a central role in eosinophil differentiation, activation and survival and has emerged as a key target for therapies treating severe asthma. The monoclonal antibodies mepolizumab and reslizumab target the ligand IL-5, preventing its interaction with eosinophils; in contrast, benralizumab binds to the IL-5 receptor (IL-5R), preventing IL-5 from binding and leading to substantially greater eosinophil reduction by enhanced antibody-dependent cell-mediated cytotoxicity. Although no direct head-to-head clinical trials of asthma have been published to formally evaluate the clinical significance of these different therapeutic approaches, the potential benefits of partial versus complete eosinophil depletion continue to remain an important area of study and debate. Here, we review the existing real-world and clinical study data of anti-IL-5/anti-IL-5R therapies in severe eosinophilic asthma.
嗜酸粒细胞性哮喘的特征是频繁恶化、症状控制不佳和肺功能加速下降。现在人们认识到，嗜酸粒细胞性哮喘的免疫反应涉及到适应性和固有免疫系统之间相互关联的复杂网络。在这个反应中，白细胞介素-5（IL-5）在嗜酸性粒细胞的分化、激活和存活中起着核心作用，并已成为治疗严重哮喘的关键靶点。单克隆抗体美泊利珠单抗和瑞利珠单抗靶向配体 IL-5，阻止其与嗜酸性粒细胞相互作用；相比之下，贝那利珠单抗结合白细胞介素-5 受体（IL-5R），阻止 IL-5 结合，并通过增强抗体依赖性细胞介导的细胞毒性导致嗜酸性粒细胞的大量减少。尽管尚未发表正式评估这些不同治疗方法临床意义的哮喘直接头对头临床试验，但部分与完全嗜酸性粒细胞耗竭的潜在益处仍然是一个重要的研究和辩论领域。在这里，我们回顾了严重嗜酸粒细胞性哮喘的抗 IL-5/抗 IL-5R 治疗的现有真实世界和临床研究数据。
