Văruț Renata Maria, Dalia Dop, Radivojevic Kristina, Trasca Diana Maria, Stoica George-Alin, Adrian Niculescu Stefan, Carmen Niculescu Elena, Singer Cristina Elena
Research Methodology Department, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania.
Department of Mother and Baby, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania.
Pharmaceuticals (Basel). 2025 Jul 10;18(7):1021. doi: 10.3390/ph18071021.
Asthma represents a heterogeneous disorder characterized by a dynamic balance between pro-inflammatory and anti-inflammatory forces, with allergic sensitization contributing substantially to airway hyperresponsiveness and remodeling. Central to its pathogenesis are cytokines such as IL-4, IL-5, IL-13, IL-17, and IL-33, which drive recruitment of eosinophils, neutrophils, and other effector cells, thereby precipitating episodic exacerbations in response to viral and environmental triggers. Conventional biomarkers, including blood and sputum eosinophil counts, IgE levels, and fractional exhaled nitric oxide, facilitate phenotypic classification and guide the emerging biologic era. Monoclonal antibodies targeting IgE (omalizumab) and IL-5 (mepolizumab, benralizumab, reslizumab, depemokimab) have demonstrated the ability to reduce exacerbation frequency and improve lung function, with newer agents such as depemokimab offering extended dosing intervals. Itepekimab, an anti-IL-33 antibody, effectively engages its target and mitigates tissue eosinophilia, while CM310-stapokibart, tralokinumab, and lebrikizumab inhibit IL-4/IL-13 signaling with variable efficacy depending on patient biomarkers. Comparative analyses of these biologics, encompassing affinity, dosing regimens, and trial outcomes, underscore the imperative of personalized therapy to optimize disease control in severe asthma.
哮喘是一种异质性疾病，其特征在于促炎和抗炎力量之间的动态平衡，过敏致敏在很大程度上导致气道高反应性和重塑。其发病机制的核心是细胞因子，如白细胞介素-4（IL-4）、白细胞介素-5（IL-5）、白细胞介素-13（IL-13）、白细胞介素-17（IL-17）和白细胞介素-33（IL-33），这些细胞因子促使嗜酸性粒细胞、中性粒细胞和其他效应细胞募集，从而在病毒和环境触发因素作用下引发发作性加重。传统生物标志物，包括血液和痰液中的嗜酸性粒细胞计数、免疫球蛋白E（IgE）水平和呼出一氧化氮分数，有助于进行表型分类并指导新兴的生物治疗时代。靶向IgE的单克隆抗体（奥马珠单抗）和靶向IL-5的单克隆抗体（美泊利单抗、贝那利珠单抗、瑞利珠单抗、德佩莫单抗）已证明能够降低加重频率并改善肺功能，像德佩莫单抗这样的新型药物给药间隔更长。抗IL-33抗体依特佩单抗能有效作用于其靶点并减轻组织嗜酸性粒细胞增多，而CM310-斯塔波基巴特、曲罗芦单抗和乐布利珠单抗抑制IL-4/IL-13信号传导的效果因患者生物标志物而异。对这些生物制剂在亲和力、给药方案和试验结果方面的比较分析强调了个性化治疗对于优化重度哮喘疾病控制的必要性。
