Costs for Patients With Alpha-1 Antitrypsin Form of COPD Are Higher, Study Says

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Researchers examined the medical costs for patients with a rare subset of chronic obstructive pulmonary disease (COPD) caused by a deficiency in alpha-1 antitrypsin receiving augmentation therapy.

Medical costs for patients with a rare subset of chronic obstructive pulmonary disease (COPD) caused by a deficiency in alpha-1 antitrypsin (AATD) receiving augmentation therapy can differ drastically, according to a recently published study.

AATD is a rare genetic disorder and causes the emphysema subtype of COPD, among other conditions. AATD is believed to affect 1 in 2000 to 5000 people worldwide. Augmentation therapy, an intravenous administration of plasma-derived alpha-1 antitrypsin protein, is the gold standard for patients with this type of COPD, the authors wrote, as it may assist with avoiding or delaying additional lung damage.

Using a large national insurance claims database in the United States, the researchers sought to identify differences between augmentation and nonaugmentation users, to calculate medical costs of patients with AATD to the insurer and to the patient, and then to evaluate changes in these costs over time.

The retrospective analysis of the direct medical costs of AATD used data from the OptumLabs Data Warehouse (OLDW), which includes de-identified claims data for privately insured and Medicare Advantage enrollees in a private US health plan. AATD patients were identified based on a diagnosis claim for AATD, an augmentation therapy claim either in a facility or home setting, or a pharmacy claim for augmentation products during the years 1993 through 2015.

The index date was the date of the first AATD-related claim. Only adult AATD patients at least 18 years of age at index date were included in the analysis. Patients over 65 for whom Medicare was the primary payer were excluded from the analysis.


The study collected patient demographics and clinical characteristics from enrollment and claims files, including age, gender, race/ethnicity, and census region. The Deyo-Charlson Comorbidity Score and presence of COPD/liver disease were calculated by capturing relevant comorbidities within 365 days before the index date.

Insurer and patient out-of-pocket (OOP) costs were calculated and categorized into the following categories: physician visits (PV), emergency department (ED) visits, inpatient (IP) stays, augmentation (AUG) therapy, other prescription drugs costs (RX), and other costs (OTH). OOP costs included the sum of co-payments, coinsurance, and deductibles.

Individuals who ever used AUG therapy (≥1 facility/pharmacy/home claim for AUG infusion) were compared with never users. For the cost comparisons, individuals were considered to be nonusers until their first claim for AUG therapy, and were considered to be AUG users thereafter.

The study cohort consisted of 9117 AATD patients and followed for 53,872 person years observed between January 1, 1993, and December 31, 2015. To the authors’ knowledge, this analysis reflects the largest ever reported cohort of patients with AATD.

For the entire cohort, the mean duration of follow-up was 5.91 years. Among AUG users and never users, the average follow-up was 5 and 6.04 years, respectively. Not-yet users were followed on average for 2 years before the start of AUG and 3 years after AUG was started.

All categories were statistically different between AUG users and nonusers (all P <.001). Within the full cohort, the main cost drivers for the insurer were PV, AUG, and IP stays.

Averaged across the entire cohort, the annual direct medical cost per person year totaled $22,975. However, the annual costs of patients with AATD differed drastically depending on AUG use status and amounted to $127,537 among users and $15,874 among nonusers (P <.001). ED spending was lower for AUG therapy users, and higher for nonusers.

Most (91%) of the augmentation users had a diagnosis of COPD. The 9% of AUG users who did not have a COPD diagnosis likely reflects the use of AUG therapy for other health conditions associated with AATD, use of AUG therapy in a manner inconsistent with guidelines, and possible issues with misdiagnosis or misclassification in this dataset.

Among the individuals who did not use AUG, 50% had a diagnosis of COPD. This finding may reflect the application of older prescribing guidelines for AUG therapy, as guidelines prior to 2015 recommended the use of AUG therapy for only a subset of cases of AATD-associated COPD. It is also possible that patient preference and cost also limited use of AUG therapy.

The researchers said a major limitation of this study is the lack of data regarding smoking status and phenotype information. Another limitation stems from the fact that only commercially insured patients of 1 large health plan were included; patients receiving healthcare services through public or other payers were not represented.


Sieluk J, Levy J, Sandhaus RA, Silverman H, Holm KE, Mullins CD. Costs of medical care among augmentation therapy users and non-users with alpha-1 antitrypsin deficiency in the United States. Chronic Obstr Pulm Dis. 2019; 6(1): 6-16. doi:10.15326/jcopdf.6.1.2017.0187.