Biologic Therapies for Severe Asthma: Current Insights and Future Directions

Abstract

Severe asthma is a subset of difficult-to-treat asthma that requires the verification of inhaler technique, the correction of modifiable risk factors, as well as diagnosis and comorbidity review. When severe asthma is suspected, patients should undergo proper phenotyping (T2-high or T2-low) and be referred to a specialized severe asthma clinic. The current biologics for severe asthma treatment include omalizumab (anti-IgE), mepolizumab and reslizumab (anti-IL-5), benralizumab (anti-IL-5 receptor), dupilumab (anti-IL-4/IL-13), and tezepelumab (anti-TSLP). The outcomes to evaluate are the reduction in systemic corticosteroid use, the reduction in exacerbations and healthcare use, and improvement in symptoms and lung function. Comorbidities should be carefully considered, and if possible, addressed with the same biologic. Dupilumab, mepolizumab, and omalizumab are also approved for chronic rhinosinusitis with nasal polyps (CRSwNP), the most common asthma comorbidity. There are currently several clinical trials on biologics for severe asthma. Depemokimab is an ultra-long-acting anti-IL-5 antibody with promising results in phase III trials as a twice-yearly biologic for T2-high asthma. Verekitug follows a similar dosing concept, targeting TSLP, but is still undergoing phase II trials. Itepekimab and astegolimab are two anti-IL-33 antibodies that could have a role in the future treatment of severe asthma. Tezepelumab is in a phase III clinical trial for CRSwNP. Besides new drugs, there is still a need for major research into biologics in severe asthma cases, namely with comparative studies, better biomarkers for predicting response, and the determination of optimal treatment duration.

Keywords: airway inflammation; asthma biomarkers; biologic therapies; difficult-to-treat asthma; non-type 2 asthma; novel asthma treatments; severe asthma; type 2 asthma.