Modifying Alpha-1 Antitrypsin Deficiency-Related Emphysema: From Evidence to Practice

Abstract

The symposium discussed the role of disease modification in alpha-1 antitrypsin deficiency (AATD)-related emphysema. Evidence from the recent RAPID trial and its extension trial showed that treating AATD patients with intravenous alpha-1 antitrypsin (alpha-1 proteinase inhibitor; [A1-PI]) therapy slowed the rate of lung density decline and had a disease-modifying effect. By modifying the course of disease, survival can be extended by several years. Dr Ferrarotti opened the symposium by introducing the topic of AATD-related emphysema, highlighting the latest epidemiological data, and providing an overview of the treatment landscape. Prof Chorostowska-Wynimko then addressed how to determine the disease modification that occurs in AATD, focussing on the clinical trial design (classical parallel-group, placebo-controlled trial design versus a ‘late-start’ study design) and clinical outcomes (forced expiratory volume in 1 second [FEV1] versus computed tomography [CT] lung density). Prof Chapman explained the results and the post hoc analyses of the RAPID trials; a sustained reduction in lung density decline rate that proves to have a disease-modifying effect. Prof Koczulla closed the symposium by relating current evidence to the real-life management of patients, notably how patients should be monitored and the prospect of home-based care.