Imaging Endpoints for Biologic Therapy in Chronic Obstructive Pulmonary Disease.

Abstract

Chronic obstructive pulmonary disease (COPD) is a leading cause of respiratory morbidity and mortality. The disease is characterized by exacerbations, which result in high symptom burden and accelerated disease progression. A subset of patients exhibit a predominant type 2 inflammatory endotype, which is associated with increased risk of exacerbation and higher responsiveness to anti-inflammatory therapy. While biologics targeting type 2 inflammation and upstream alarmins have shown promise in reducing exacerbations and improving lung function, there is a need for clinical trial endpoints that reflect potential disease modification and enable anunderstanding of the mechanisms by which biologics may help patients with COPD. Measures of lung disease on imaging, including airway wall thickness, mucus plugging, and ventilation defect percentage, appear to be modifiable in response to therapy with biologics. The evidence base for treatment effects is derived largely from trials in asthma, but the findings can be extrapolated to COPD. Imaging endpoints have the potential to markedly decrease sample size requirements for clinical trials testing the effect of biologics on structural remodeling in COPD.