Lessons learned regarding optimal use of biologics to achieve disease remission in severe asthma

Abstract

Severe asthma management has changed dramatically in the last decade after the introduction of T2-directed biologic therapies. This has enabled more ambitious treatment goals, including on-treatment clinical remission in severe asthma. Definitions of clinical remission have invariably included absence of both systemic corticosteroids for disease control and asthma exacerbations but have varied regarding the level of required symptom control and optimal lung function; a single definition would allow a better understanding of the longer-term impact of achieving clinical remission in both clinical practice and research studies. Studies have revealed that a few patients with severe asthma achieve clinical remission, and key barriers have been identified, including those associated with disease-related airway damage, such as fixed airflow obstruction associated with high symptom burden, and comorbidities including those from corticosteroid toxicity, such as obesity, anxiety, and depression. Earlier intervention with biologic therapy has been proposed as a potential method to overcome these barriers, tackling the T2 inflammation before disease and corticosteroid-related damage are established. However, biologic therapy should not be considered a panacea, and appropriate patient selection remains key to ensuring their optimal use. T2 biomarker–guided therapy allows clinicians to correlate clinical manifestations to the underlying biological etiology. Biomarker-guided biologic therapy alongside treatment of non–T2-driven disease may improve clinical remission attainment rates. Conversely, the presence of ongoing T2 inflammation alongside on-treatment clinical remission raises questions regarding the long-term effect of subclinical inflammation.