Dosing and delivery of Alpha-1 Antitrypsin augmentation therapy in US patients with Alpha-1 Antitrypsin Deficiency

Abstract

Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disorder that predisposes individuals to early-onset pulmonary emphysema. Augmentation therapy is the only disease-specific treatment available, yet its delivery varies widely across clinical settings. This study aimed to evaluate current augmentation therapy practices in the United States, focusing on infusion location, administration methods, side effects, exacerbation frequency, and mortality outcomes. A retrospective cohort design was employed using data from 2,904 patients enrolled in AlphaNet’s support programme between 2008 and 2015. Patients received therapy across five infusion settings: home, hospital, standing infusion centres, doctor’s offices, and workplaces. Descriptive statistics, Kruskal-Wallis tests, and binary logistic regression were used to assess associations between treatment location and clinical outcomes. Home-based therapy was the most common setting (66.8%), followed by hospital-based care (23.7%). Significant differences were observed in age, genotype distribution, administration method, and follow-up frequency across infusion locations. Patients treated in hospitals and standing infusion centres were older and had more complex clinical profiles. Needle stick access was predominant, while port-based access was more frequent in clinical settings. Mortality analysis revealed that patients treated at home had the youngest mean age at death, while those treated in doctor’s offices had the longest survival time. Logistic regression identified age, exacerbation frequency, and infusion location as significant predictors of mortality. Each additional year of age and exacerbation increased mortality risk by 4.9% and 20.7%, respectively. The findings suggest that infusion location may reflect underlying patient complexity rather than directly influencing outcomes. Despite limitations in clinical data and temporal precision, this study provides valuable insights into real world AATD management and supports the growing role of home-based therapy in personalized care.