Therapeutics for severe asthma

Abstract

Purpose: Although severe asthma affects fewer than 10% of patients with asthma, it accounts for a disproportionately high burden of morbidity, mortality, and healthcare costs. It is defined by persistent symptoms and frequent exacerbations despite high-step pharmacologic therapy. Patients with severe asthma also experience marked impairment in quality of life and are at increased risk of adverse effects associated with long-term systemic corticosteroid use. Current Concepts: Asthma is now recognized as a heterogeneous disease with multiple phenotypes, among which type 2 (T2) inflammation is central in many severe cases. Recent advances have enabled the development of biologic therapies targeting key T2 pathways, including immunoglobulin E, interleukin (IL)-5, IL-5 receptor α, IL-4 receptor α, and thymic stromal lymphopoietin. The identification of biomarkers—such as elevated blood or sputum eosinophils, increased fractional exhaled nitric oxide, and allergen-driven responses—is crucial for guiding biologic selection and improving disease control. Discussion and Conclusion: Effective management of severe asthma requires a stepwise approach: confirming the diagnosis, addressing modifiable risk factors, optimizing inhaler technique, and initiating biologic therapy according to T2 inflammation status. Conventional add-on treatments such as theophylline, leukotriene receptor antagonists, and long-acting muscarinic antagonists have shown limited efficacy and often necessitate ongoing oral corticosteroid use, with its attendant adverse effects. The introduction of biologics has significantly improved clinical outcomes, reducing exacerbation rates, enhancing symptom control and lung function, and lessening dependence on oral corticosteroids in patients with severe asthma.