Clinical remission in severe asthma treated with biologics and macrolides: Definition, prevalence, associated factors, and future perspectives

Severe asthma is associated with persistent symptoms, frequent exacerbations, oral corticosteroid dependence, and reduced lung function. The emergence of biologic therapies targeting type 2 (T2) cytokines, including IL-5, IL-4, IL-13, thymic stromal lymphopoietin, and circulating IgE, has changed disease management and led to substantial improvement. This approach has also introduced the concept of clinical remission (defined as controlled symptoms, no maintenance corticosteroid use, no exacerbations, and optimized/stabilized lung function) as a potential treatment target. Although some guidelines propose remission criteria, no universally accepted definition exists, and reported prevalence varies depending on definitions, and therapies, and patient groups. Clinical remission has been achieved in approximately one-third of patients receiving T2-targeted biologics. Factors associated with achieving clinical remission include less severe disease (less symptoms, fewer exacerbations, and better lung function), fewer comorbidities (e.g. obesity, anxiety/depression), greater T2-disease activity (the presence of nasal polyps and higher T2 biomarkers), and early treatment response. Azithromycin therapy can also contribute to achieving remission in both T2-high and T2-low moderate to severe asthma phenotypes. Future perspectives on asthma remission include integrating a treatable traits approach, establishing and validating the definition of complete remission, and assessing the long-term benefits of achieving remission. Complete remission may encompass clinical remission, inflammatory remission (normalization of T2 biomarkers), and structural/functional remission (resolution of bronchial hyperresponsiveness, mucus plugging, and airway remodeling). Standardizing remission criteria will enable the identification of predictive factors and facilitate personalized, treat-to-target strategies. Early induction of clinical remission may be a promising strategy for optimizing outcomes in severe asthma.