Monoclonal Antibodies May Be Significant in the Treatment of Severe Asthma

Image credit: fourtakig | stock.adobe.com

For asthma, a common and burdensome chronic inflammatory airway disease, the main concern is the manifestation of irreversible tissue remodeling of the airways because of the chronic inflammatory environment which can disrupt the airways’ structure. The most common treatment options for those who have troublesome asthma are inhaled corticosteroids or muscle relaxants; however, the development of steroid resistance is a common issue. A recent review published in Clinical and Experimental Allergy shows that when monoclonal antibodies are administered to patients who have severe asthma, symptoms are prevented from becoming aggravated.^1,2

In their review, the investigators highlighted current updates on the interleukin (IL)-5 signaling pathway and its role in asthma pathophysiology as well as its utilization as a therapeutic agent for asthma. Additionally, they summarize the airway remodeling that is associated with asthma and the potential role IL-5 has in airway remodeling.²

Airway remodeling involves structural changes of both the small and large airway walls because of repeated cycles of injury and repair as a result of chronic inflammation in patients who have chronic lung diseases, such as asthma. Although it was initially believed to start in advanced stages of disease, it may occur during earlier phases of the disease, prior to symptom manifestations. Structural modifications during airway modification can consist of the following: epithelial layer alteration; subepithelial fibrosis, such as fibrotic layer composition; increased airway smooth muscle mass; goblet cell hyperplasia and mucus hypersecretion; and angiogenesis.¹

Additionally, the release of IL-5 is strongly associated with eosinophilia by acting primarily on cells of eosinophilic origin, where it stimulates growth and differentiation, improves survival, and promotes the release of granular contents at the site of inflammation. In asthma, IL-5 is a potent pro-inflammatory cytokine, and its elevation mediates the recruitment of eosinophils to the airways, maturation, activation, differentiation, and survival.¹

According to the experts, conventional treatments—such as steroids—mainly target inflammation, rather than remodeling, whereas emerging therapies that focus on specific receptors or cytokines would be more promising in the alleviation of severe chronic disease like asthma. Though corticosteroids have previously been the most effective in treating asthma, the investigators noted that using monoclonal antibodies demonstrated promising results in recent studies, and the administration of these has led to reduced asthma exacerbations, lower eosinophilia, and decreased airway remodeling.^1,2

“Biological therapies are a promising therapeutic approach for people with steroid-resistant asthma…[they are] recently gaining a lot of attention as a biological target relevant to the tissue remodeling process,” said the study authors in a news release.²

In asthma, monoclonal antibodies block the interaction of IL-5 with its receptor by preventing ligand-receptor binding and, therefore, the resulting activation of the downstream signaling pathway. This further inhibits amplification of the signal resulting in apoptosis of eosinophils as well as basophils, to an extent. The antibodies, according to the experts, include mepolizumab (Nucala; GSK), reslizumab (Cinqair, Teva Pharmaceuticals), and benralizumab (Fasenra; AstraZeneca).¹

In research, the administration of these antibodies resulted in reduced asthma exacerbations, decreased airway remodeling, and lower eosinophilia. Additionally, because there is limited understanding of IL-5’s mechanistic role in airway remodeling, more advanced research is necessary.^1,2

“Further research…should target transcriptomics, proteomics, and second harmonic analysis of patient samples analyzed pre- and post-anti-IL5 therapy [to understand] the underlying molecular pathways impacted by IL-5 and to identify it as a potential biomarker for improved targeted therapies,” said the authors in the news release.²

REFERENCES

1. AbuJabal R, Ramakrishnan RK, Bajbouj K, Hamid Q. Role of IL-5 in asthma and airway remodelling. Clin Exp Allergy. 2024; 54: 538-549. doi:10.1111/cea.14489

2. University of Sharjah. Monoclonal antibodies have the potential to treat severe asthma bouts, scientists find. News release. October 21, 2024. Accessed October 23, 2024. https://www.eurekalert.org/news-releases/1061988