Respiratory Medicine Department, University Hospital Virgen de las Nieves, 18014 Granada, Spain.
Pharmacy Service, Pharmacogenetics Unit, University Hospital Virgen de las Nieves, 18014 Granada, Spain.
Int J Mol Sci. 2023 Jan 19;24(3):2011. doi: 10.3390/ijms24032011.
Severe Uncontrolled Asthma (SUA) counts for more than 25% of cases of severe asthma. The main factors that impair the quality of life of these patients are high doses of oral corticosteroids, the presence of exacerbations, and reduced lung function. The objective of this study was to evaluate, in real life, the clinical improvement of patients with SUA treated with anti-interleukin 5 (IL5) therapies: mepolizumab and benralizumab, together with the search for biomarkers associated with the response. We conducted a retrospective observational cohort study that included patients with severe uncontrolled eosinophilic asthma in a tertiary hospital receiving biological therapies. Three types of response were evaluated: improvement in lung function, reduction in exacerbations, and decrease in the use of oral corticosteroids. After 12 months of treatment, significant reductions were found in the number of exacerbations, the use of oral corticosteroids, and blood eosinophil levels for both biological therapies ( < 0.001). Lung function improved, achieving a significant improvement in %FEV1 ( < 0.001), as well as asthma control, with a significant increase in asthma control test (ACT) scores in both therapies. The markers associated with the corticosteroid-saving effect were the low doses of oral corticosteroids and absence of exacerbations for mepolizumab, and higher blood eosinophilia, absence of chronic obstructive pulmonary disease (COPD), and reduction in oral corticosteroid cycles for benralizumab. The greatest improvement in lung function in both therapies was linked to lower previous FEV1 levels and absence of other respiratory diseases. The reduction in exacerbations was associated with absence of exacerbations the previous year for mepolizumab and never smokers for benralizumab. The results of this real-life study confirm the clinical benefit obtained after the introduction of an anti-IL5 biological therapy and the possible predictive biomarkers of response to treatment.
严重未控制哮喘（SUA）占严重哮喘病例的 25%以上。这些患者生活质量受损的主要因素是大剂量口服皮质类固醇、发作频繁和肺功能下降。本研究的目的是在现实生活中评估 SUA 患者接受抗白细胞介素 5（IL5）治疗（美泊利珠单抗和贝那利珠单抗）后的临床改善情况，并寻找与治疗反应相关的生物标志物。我们进行了一项回顾性观察队列研究，纳入了在一家三级医院接受生物治疗的重度未控制嗜酸粒细胞性哮喘患者。评估了三种类型的反应：肺功能改善、减少发作次数和减少口服皮质类固醇的使用。治疗 12 个月后，两种生物治疗均显著减少了发作次数、口服皮质类固醇的使用量和血嗜酸性粒细胞水平（均<0.001）。肺功能得到改善，实现了%FEV1的显著提高（<0.001），以及哮喘控制的改善，两种治疗方法的哮喘控制测试（ACT）评分均显著增加。与皮质类固醇节省效应相关的标志物是美泊利珠单抗的低剂量口服皮质类固醇和无发作，以及贝那利珠单抗的较高血嗜酸性粒细胞、无慢性阻塞性肺疾病（COPD）和口服皮质类固醇周期减少。两种治疗方法中肺功能的最大改善与较低的既往 FEV1水平和无其他呼吸系统疾病有关。减少发作次数与美泊利珠单抗前一年无发作和贝那利珠单抗从未吸烟者有关。这项真实生活研究的结果证实了在引入抗 IL5 生物治疗后获得的临床获益，以及治疗反应的可能预测生物标志物。
