Del-Barrio-Buesa Silvia, Narrillos-Moraza Álvaro, García-de-Pedro Julia, de-Castro-Martínez Francisco Javier, Durán-García María Esther, Escudero-Vilaplana Vicente, Lobato-Matilla Elena, Romero-Jimenez Rosa, Chamorro-de-Vega Esther, Ruiz-Briones Paula, Garcia-Moreno Félix Jesús, Martín-Bartolomé María, Herranz Ana, Sanjurjo María
Department of Pharmacy, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
Front Med (Lausanne). 2025 Aug 11;12:1635688. doi: 10.3389/fmed.2025.1635688. eCollection 2025.
Uncontrolled severe asthma represents a substantial clinical and economic burden, particularly in patients with comorbidities and poor response to high-dose inhaled corticosteroids. Monoclonal antibodies targeting type 2 (T2) inflammation have become key therapeutic options, but their real-world performance remains insufficiently characterized.
To evaluate the real-world effectiveness, adherence, and persistence of benralizumab, mepolizumab, omalizumab, and reslizumab in adults with uncontrolled severe asthma after 12 months of treatment.
A retrospective real-world observational study was conducted in patients with uncontrolled severe asthma who initiated treatment with benralizumab, mepolizumab, omalizumab, and reslizumab between January 2015 and December 2022. Clinical, functional, and laboratory outcomes were assessed at baseline and after 12 months, including eosinophil count, forced expiratory volume in 1 s (FEV), fractional exhaled nitric oxide (FeNO), Asthma Control Test (ACT) score, exacerbations frequency, emergency visits, hospitalizations, adherence, and treatment persistence. Data were extracted from the electronic health record and results are presented as median values with interquartile ranges (IQR).
A total of 154 patients (188 treatment episodes) were included. The median follow-up was 2.2 years (IQR 1.3-4.2). All monoclonal antibodies were associated with significant improvements in asthma control at 12 months. Blood eosinophil counts declined across all therapies, with near-complete depletion observed in patients treated with benralizumab and reslizumab. Median ACT scores increased by six points, and FEV₁ improved by 7%. Annual exacerbation rates and healthcare utilization decreased significantly across all groups. Adherence was high (95%), and the median treatment persistence was 2.0 years (IQR 1.4-4.1). Overall, 42% of patients discontinued treatment, mainly due to insufficient clinical response (48.4%) or drug supply issues (42.2%).
In routine clinical practice, benralizumab, mepolizumab, omalizumab, and reslizumab were associated with improvements in asthma control, lung function, and reduction in exacerbations over 12 months. Benralizumab and reslizumab were associated with the greatest reductions in eosinophil counts. Our findings suggest comparable effectiveness across biologics. High adherence and treatment persistence support their feasibility in real-world settings. These results underscore the relevance of phenotype-driven therapy selection and highlight the need for long-term monitoring to optimize outcomes in severe asthma management.
未得到控制的重度哮喘带来了巨大的临床和经济负担，尤其是在合并其他疾病且对高剂量吸入性糖皮质激素反应不佳的患者中。靶向2型（T2）炎症的单克隆抗体已成为关键的治疗选择，但其在实际临床中的表现仍未得到充分描述。
评估贝那利珠单抗、美泊利珠单抗、奥马珠单抗和瑞利珠单抗在治疗12个月后对未得到控制的重度哮喘成人患者的实际疗效、依从性和持续性。
对2015年1月至2022年12月期间开始使用贝那利珠单抗、美泊利珠单抗、奥马珠单抗和瑞利珠单抗治疗的未得到控制的重度哮喘患者进行了一项回顾性实际临床观察研究。在基线和12个月后评估临床、功能和实验室指标，包括嗜酸性粒细胞计数、第1秒用力呼气量（FEV₁）、呼出一氧化氮分数（FeNO）、哮喘控制测试（ACT）评分、加重频率、急诊就诊次数、住院次数、依从性和治疗持续性。数据从电子健康记录中提取，结果以中位数和四分位数间距（IQR）表示。
共纳入154例患者（188个治疗疗程）。中位随访时间为2.2年（IQR 1.3 - 4.2）。所有单克隆抗体在12个月时均与哮喘控制的显著改善相关。所有治疗组的血液嗜酸性粒细胞计数均下降，接受贝那利珠单抗和瑞利珠单抗治疗的患者嗜酸性粒细胞几乎完全清除。ACT评分中位数增加了6分，FEV₁提高了7%。所有组的年度加重率和医疗资源利用率均显著下降。依从性较高（95%），中位治疗持续时间为2.0年（IQR 1.4 - 4.1）。总体而言，42%的患者停止治疗，主要原因是临床反应不足（48.4%）或药物供应问题（42.2%）。
在常规临床实践中，贝那利珠单抗、美泊利珠单抗、奥马珠单抗和瑞利珠单抗与12个月内哮喘控制的改善、肺功能的提高以及加重次数的减少相关。贝那利珠单抗和瑞利珠单抗与嗜酸性粒细胞计数的最大降幅相关。我们的研究结果表明各生物制剂的疗效相当。高依从性和治疗持续性支持它们在实际临床环境中的可行性。这些结果强调了基于表型驱动的治疗选择的相关性，并突出了长期监测以优化重度哮喘管理结果的必要性。
