PRO60 Clinical and Economic Burden Associated with ALPHA-1 Antitrypsin Deficiency (AATD) in Adults: Systematic and Targeted Literature Reviews

AATD is a rare genetic disorder characterized by reduced circulating AAT protein levels leading to a higher risk of developing emphysema. Due to a paucity of recent publications comprehensively assessing the burden of AATD, literature reviews were conducted in six key areas, including A) epidemiology, B) clinical burden due to disease complications (targeted reviews) and C) economic burden (systematic review). EMBASE®, MEDLINE®, Cochrane library, EconLit, and Tufts CEA Registry databases were collectively searched (database inception-June 2020) for studies on AATD. Congress proceedings (ERS, ATS, Euro-Global Gastroenterology Conference, International Conference on Pulmonology and Lung Health, ISPOR, and ISPOR Europe, 2017-2020) and registry websites (including REDAAT and EUROCAT) were also searched. References were screened at abstract and full-text level by 2-3 independent reviewers. Searches identified 19, 22, and 11 publications relating to A, B, and C, respectively. Individuals with the Pi*ZZ genotype, which increases mortality risk, were mainly in Europe (∼120,000) and the United States (Caucasians of European descent; ∼70,000). Pulmonary AATD manifestations occurred frequently (52%; total number of patients assessed, N=5109) and were associated with lung function decline for patients with severe AATD. Lung and liver disease were prevalent severe AATD complications; in 5 publications in the B category, 27% (N=497), 52% (N=1132), and 79% (N=312) of cases had lung disease and 10% (N=1595), 10% (N=312), and 35% (N=94) had liver disease. In another study, 15% of patients had anxiety and 18% had depression (N=33). For patients with AATD versus those with non-AATD-associated chronic obstructive pulmonary disease (COPD), length of hospital stay due to COPD was 14% longer, and inpatient cost and total healthcare costs/patient were $1,487 and $27,674 higher, respectively. AATD is associated with significant disease complications and increased healthcare costs. Addressing the unmet need for increased awareness and appropriate therapies may help reduce these burdens.