Economic burden review: cost and resource use associated with alpha-1 antitrypsin deficiency (AATD)

First author, year [ref.]CountrySubjects nCost-yearHealthcare costHealthcare resource useMain economic burden outcomes
Herrera, 2021 [43]USA51092017Median (IQR) annual total healthcare costs USD 9753 (3070–45 266)
Median (IQR) total medical costs USD 4927 (1569–16 340)
Median (IQR) total pharmacy costs USD 2063 (214–10 000)
Mean±sd annual number of visits:
ER visits: 0.5±2.4
Inpatient visits: 0.6±2.7
Outpatient visits: 6.4±12.1
Other visits: 2.0±7.3
Patients with severe AATD-related pulmonary manifestations requiring hospitalisation are substantially burdened by higher healthcare resource use.
Rozario, 2019 [113]USANRNRImpact of a missed AAT therapy dose on total monthly healthcare costs (not including AAT therapy cost)
With dose: USD 1862
Without dose: USD 2100
Difference: +USD 238
NRThe increased cost for patients with AATD who missed a dose of AATD therapy was possibly due to the higher downstream systemic healthcare costs that are associated with nonadherence to therapy.
Sieluk, 2018 [105]USA91172017Annual direct costs for AAT therapy users:
Total: USD 127 537
Physician visits: USD 15 064
AAT therapy: USD 82 002
NRThere were higher costs for AAT therapy users for all cost drivers (physician and emergency visits, inpatient stays, AAT therapy and other drugs). A consistent trend of increasing cost was observed between 1993 and 2015, although inpatient and physician visit costs remained steady over the last 10 years of the study.
Choate, 2019 [44]USA3535NRNRAnnual visits SZ versus ZZ genotypes of AATD#
Primary physician visits: 3.7 versus 3.1
Lung specialist visits: 3.2 versus 2.9
Hospitalisations: 0.8 versus 0.6
Patients with a PiSZ genotype reported more primary physician visits (p<0.001), lung specialist visits (p<0.001) and hospitalisations (p=0.012) than patients with a PiZZ genotype.
Attaway, 2019 [60]USA8039NRNRHospitalisation
average length of stay: 5.3 days
There was a stable low rate of in-hospital mortality throughout the study (2004–2014).
Aggarwal, 2018 [109]USA14932015Hospitalisation
Overall cost per stay: USD 50 612
0–18 years: USD 120 026
18–45 years: USD 39 192
45–59 years: USD 53 118
>60 years: USD 48 613
Mean length of stay: 5.43 days
0–18 years: 8 days
18–45 years: 4.4 days
45–59 years: 5.6 days
>60 years: 5.4 days
Higher inpatient costs in the USA were reported for adults aged ≥45 years with AATD compared with adults aged <45 years based on national inpatient data.
Karl, 2017 [75]Germany1312012Annual direct cost for AATD patients diagnosed with COPD (excluding AAT therapy cost)
Patients receiving AAT therapy: EUR 7117
Patients not receiving AAT therapy: EUR 6099
Annual indirect costs (human capital approach)
Patients receiving AAT therapy: EUR 18 813
Patients not receiving AAT therapy: EUR 16 171
AATD patients diagnosed with COPD versus those with COPD alone
Outpatient visits: two-fold higher with AATD
Hospitalisation: 24% versus 39%
Inpatient length of stay: 2.3 versus 5.8 days
Patients with AATD receiving AAT therapy versus those without
Inpatient length of stay: 2.2 versus 2.7 days
For patients with AATD in Germany, annual direct medical costs in 2012 were higher for those receiving AAT therapy than for those not on AAT therapy. The study excluded the mean annual AAT therapy cost of EUR 72 255. Indirect costs were based on a human capital approach that considered full labour costs for all sick days and premature retirement at age <65 years.
Greulich, 2017 [106]Germany590NRNRConsultations and hospitalisation rates higher in patients with AATD than in matched patients in reference groups (COPD, emphysema or asthma)When compared with non-AATD patients diagnosed with COPD, AATD patients had significantly more consultations.
Zacherle, 2015 [107]USA279NRTotal annual healthcare costs AATD versus COPD
USD 27 674 greater for AATD
Annual visits AATD versus COPD
Emergency: 58.4% versus 42.5%
Inpatient: 58.0% versus 19.5%
Higher mean annual costs were reported for AATD patients diagnosed with COPD versus those with general COPD (p<0.001); 13% of the AATD cohort were receiving AAT therapy.
Blanchette, 2015 [110]USA6842009Mean hospitalisation cost
Age 20–39 years: USD 13 820
Age >80 years: USD 16 079
Mean hospital stay
Age 20–39 years: 5.0 days
Age >80 years: 8.2 days
There was an increased cost for AATD inpatients versus general COPD patients (+USD 1487 per stay; p=0.0251).
Barros-Tizón, 2012 [111]Spain127NRHospitalisation cost before AAT therapy use versus after
Savings per patient: EUR 417
Savings in patients with exacerbations: EUR 907
Hospitalisation with versus without AAT therapy
Length of stay with no exacerbations: 3.0 versus 3.9 days
Length of stay with exacerbations: 4.6 versus 6.7 days
There were substantial hospitalisation-derived cost savings in patients who were treated with AAT therapy.
Dye, 2011 [112]Australia5582007–2008Direct cost
Hospitalisation per patient: USD 36 764
Per admission: USD 7145
Hospital admissions
5.14 per patient over 6 years
AATD was reported to be one of the most expensive single-gene and chromosome disorders evaluated in this study.
Mullins, 2003 [114];
Mullins, 2001 [115]
USA6881998Direct costs associated with treatment+, physician visits, emergency department visits and hospitalisation
Annual: USD 36 471
PiZZ: USD 38 632
Non-PiZZ: USD 30 604
Physician visits: 8.5 per yearSelf-reported medical costs were higher for patients with a PiZZ genotype versus non-ZZ individuals. AAT therapy was the major driver of self-reported cost.
1997–1999Total annual healthcare costs associated with all medical
visits, medications, and all other expenditures (e.g. emergency department visits)
PiZZ: USD 30 948
Non-PiZZ: USD 20 673
NRAnnual healthcare costs for patients with ZZ AATD were high versus non-ZZ, whether they were receiving augmentation therapy or not.
Piitulainen, 2003 [104]Sweden52002Annual direct cost associated with AAT therapy
Tailored dose: SEK 1 560 400
Standard dose: SEK 2 600 000
NRTailored pharmacokinetic dosing of human AAT reduces the total annual dose and cost of i.v. AAT therapy.
Stoller, 2000 [116]USA7121997–1999NRResource use (number of physician visits)The mean±sd number of physician visits reported by patients with AATD was 7.8±9.4 per year.
Stone, 2020 [117]USA12582011–2017After adjustment, compared with pre-diagnosis (USD 24 782±161 896), median±sd total healthcare costs were USD 9962 greater (USD 34 744±80 792; p<0.05) in year 1 post-diagnosis; USD 3703 less (USD 21 079±51 186; p>0.05) in year 2; and USD 12 567 less (USD 12 215±46 594; p>0.05) in year 3
Adjusted median±sd medical costs in the pre-diagnosis year were USD  10 825±89 936; USD 2304 greater (USD 13 129±52 953); p>0.05) in year 1; USD 791 less (USD 10 034±26 600; p<0.05) in year 2; and USD 5186 less (USD 5639±9838; p<0.05) in year 3
Adjusted median±sd number of inpatient events per patient in the pre-diagnosis year were 0.34±0.75; 26% less (0.27±0.58; p<0.05) in year 1; 240% less (0.10±0.42); p<0.05) in year 2; and 340% less (0.00±0.35; p<0.05) in year 3 post-diagnosisHealthcare costs increased in the first year following diagnosis of AATD; however, they decreased in subsequent years, primarily due to the reduction of inpatient admissions and medical costs.
Sieluk, 2020 [108]USA88812000–2017Adjusted total all-healthcare cost ratios for AATD patients diagnosed with COPD versus controls were 2.04 (95% CI 1.60–2.59) and 1.98 (95% CI 1.55–2.52), while the incremental cost difference totalled USD 6861 (95% CI 3025–10 698) and USD 5772 (95% CI 1940–9604) per patient before and after the index date, respectivelyAATD patients diagnosed with COPD had higher expenditures and use of office visits and other services, as well as office visits, outpatient, ER and prescription drugs before and after the index date, respectively12 months before and after their initial COPD diagnosis, patients with AATD incurred higher healthcare utilisation costs that were double the cost of similar COPD patients without AATD. Increased costs of AATD-associated COPD were not solely attributable to AAT therapy use.
Rueda, 2020 [118]USA68322010–2015The introduction of a DMP was estimated to decrease costs of the management of patients with AATD by USD 13.5 million over 5 yearsThe savings attributed to the programme were due to 2555 exacerbations, 5180 ER visits, 9342 specialist visits and 105 358 GP visits avoidedA comprehensive DMP for a rare condition might provide cost savings to a health plan. BIAs for rare disease may be more informative if they focus on DMPs rather than on individual drugs.
Borget, 2020 [119]France3652014–2017Mean annual cost per patient was EUR 13 680 (excluding AAT therapy) driven by ambulatory-related costs (45%) and hospital-related costs (35%). Paid sick time represents 20% of the total annual cost.This was the first study to evaluate the number of patients treated and the economic burden of AATD in France.
Sieloff, 2021 [120]USA2002–2014In 2014, hospitalisation costs adjusted to 2020 dollars for AATD was USD 108 million relative to all annual NIS dischargesAATD was associated with the greatest number of hospitalisations of all the genetic liver diseases over the 12-year study period for both NACLD and NALC.
Lee, 2020 [121]USA1872 AATD-related cirrhosis, 7488 non-AATD-related cirrhosis2011–2017Hospitalisation costs for AATD-related cirrhosis versus non-AATD-related cirrhosis (USD 72 406 versus USD 59 386; p=0.38)There was no difference in hospitalisation costs for AATD-related cirrhosis versus non-AATD-related cirrhosis.

IQR: interquartile range; ER: emergency room; NR: not reported; AAT: alpha-1 antitrypsin; PiSZ/ZZ: Pi (or SERPINA1 gene) SZ and ZZ alleles; i.v.: intravenous; DMP: disease management programme; GP: general practitioner; BIA: budget impact analysis; NIS: National Inpatient Sample; NACLD: nonalcoholic chronic liver disease; NALC: nonalcoholic liver cirrhosis. #: a greater proportion of ZZs than SZs received AAT therapy (93.5% versus 87.1%, p<0.001); : total direct costs do not include AAT therapy costs; +: values given as 1998 USD.