Monoclonal antibodies in severe asthma: outcomes from real-world data

Silvia del-Barrio-Buesa¹Álvaro Narrillos Moraza¹Julia García de Pedro^2,3Javier de Castro Martínez⁴María Esther Duran-Garcia¹Vicente Escudero-Vilaplana^1*Elena Lobato-Matilla¹Rosa Romero-Jimenez¹Esther Chamorro-de-Vega¹Paula Ruiz Briones¹Félix Moreno García¹María Martín Bartolomé¹Ana Herranz¹María Sanjurjo¹

• ¹Department of Hospital Pharmacy. Hospital General Universitario Gregorio Marañón. Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
• ²Department of Pneumology. Hospital General Universitario Gregorio Marañón. Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
• ³Department of Medicine. Universidad Complutense de Madrid, Madrid, Spain
• ⁴Department of Allergy. Hospital General Universitario Gregorio Marañón. Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain

Background: 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. Objective: To evaluate the real-world effectiveness, adherence, and persistence of benralizumab, mepolizumab, omalizumab, and reslizumab in adults with uncontrolled severe asthma after twelve months of treatment. Methods: 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 twelve months, including eosinophil count, forced expiratory volume in one second (FEV1), 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). Results: 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%). Conclusions: 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.