Antibodies | Recent Developments in Monoclonal Antibody-Based Biologic Therapy for Severe Refractory Eosinophilic Asthma

This article systematically summarizes the application progress of monoclonal antibody-based biologic therapies targeting IL-5, IL-4, and IL-13 in severe refractory eosinophilic asthma, emphasizing the critical role of non-invasive biomarkers in patient stratification and treatment selection. Additionally, it evaluates the clinical efficacy, safety, and future directions of these biologic therapies, providing scientific evidence for precision treatment.

 

Literature Overview

The article titled 'Recent Developments in Monoclonal-Antibody-Based Biologic Therapy for Severe Refractory Eosinophilic Asthma', published in the journal 'Antibodies', reviews and summarizes the current application of biologics targeting the T2 inflammatory pathway in treating severe eosinophilic asthma, highlighting the value of biomarkers such as blood eosinophil counts, FeNO, and serum periostin in guiding treatment decisions.

Background Knowledge

Asthma is a highly heterogeneous chronic airway inflammatory disease, among which the T2-high phenotype accounts for approximately 50%. This phenotype is characterized by elevated IgE levels and eosinophilic infiltration driven by cytokines such as IL-4, IL-5, and IL-13. Traditional treatment relies on inhaled corticosteroids (ICS) and long-acting β2-agonists (LABA), but approximately 5% of patients remain uncontrolled and require oral corticosteroids (OCS). However, long-term OCS use is associated with multiple side effects. Therefore, biologics targeting T2 cytokines, such as anti-IL-5, anti-IL-5R, and anti-IL-4/13 agents, have become important therapeutic options. Current research focuses on how to precisely identify patients who can benefit from non-invasive biomarkers (e.g., FeNO, blood eosinophil count) to optimize treatment strategies and reduce unnecessary biologic therapy usage.

 

 

Research Methods and Experiments

This article is a systematic review summarizing clinical evidence on monoclonal antibody therapies targeting IL-5 and IL-4/13 in severe eosinophilic asthma, based on English literature from PubMed and Medline. The review highlights the application of biomarkers such as blood eosinophils, FeNO, and serum periostin in patient phenotyping, and analyzes the dosage, efficacy, and safety of different biologics across studies.

Key Conclusions and Perspectives

• Anti-IL-5 monoclonal antibodies (e.g., mepolizumab, reslizumab, benralizumab) significantly reduce acute exacerbations of eosinophilic asthma, decrease OCS use, and improve lung function and quality of life.
• Dupilumab, an anti-IL-4Rα monoclonal antibody, effectively reduces acute exacerbations and improves lung function by dual blockade of IL-4 and IL-13 signaling.
• Non-invasive biomarkers such as FeNO, blood eosinophil count, and serum periostin provide valuable guidance for clinical decision-making, helping to avoid unnecessary airway sampling.
• Some patients do not respond to initial biologic therapy and may require switching to other T2-targeted agents, underscoring the importance of personalized treatment.
• Although T2-targeted therapies are highly effective in some patients, they are ineffective in those with the T2-low phenotype, highlighting the necessity of asthma phenotyping for treatment selection.

Research Significance and Prospects

This review highlights the need for more studies in the pediatric population and head-to-head comparisons of biologics to achieve long-term disease remission. It also points out that current biomarkers have limited utility in enhancing treatment response, suggesting that novel T2-independent therapeutic strategies, such as targeting upstream signals like IL-33 and TSLP, should be explored to expand treatment indications and improve efficacy prediction.

 

 

Conclusion

This article systematically reviews recent advances in biologics targeting T2 inflammation in severe eosinophilic asthma. Monoclonal antibodies against IL-5 and IL-4/13 demonstrate promising efficacy in reducing acute exacerbations, improving lung function, and decreasing reliance on OCS. Biomarkers such as blood eosinophil counts, FeNO, and serum periostin offer valuable tools for clinical management. However, a subset of patients still fails to respond to current therapies, indicating the need for broader target exploration and more personalized treatment strategies. Moreover, the high cost and limitations in predicting therapeutic response warrant further optimization to enable more precise and efficient biologic treatment for asthma.

 

Garry M Walsh. Recent Developments in Monoclonal-Antibody-Based Biologic Therapy for Severe Refractory Eosinophilic Asthma. Antibodies.