Economic burden review: cost and resource use associated with alpha-1 antitrypsin deficiency (AATD)
| First author, year [ref.] | Country | Subjects n | Cost-year | Healthcare cost | Healthcare resource use | Main economic burden outcomes |
| Herrera, 2021 [43] | USA | 5109 | 2017 | Median (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] | USA | NR | NR | Impact 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 | NR | The 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] | USA | 9117 | 2017 | Annual direct costs for AAT therapy users: Total: USD 127 537 Physician visits: USD 15 064 AAT therapy: USD 82 002 | NR | There 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] | USA | 3535 | NR | NR | Annual 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] | USA | 8039 | NR | NR | Hospitalisation 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] | USA | 1493 | 2015 | Hospitalisation 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 | Hospitalisation 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] | Germany | 131 | 2012 | Annual 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] | Germany | 590 | NR | NR | Consultations 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] | USA | 279 | NR | Total 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] | USA | 684 | 2009 | Mean 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] | Spain | 127 | NR | Hospitalisation 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] | Australia | 558 | 2007–2008 | Direct 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] | USA | 688 | 1998 | Direct 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 year | Self-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. |
| 1997–1999 | Total 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 | NR | Annual healthcare costs for patients with ZZ AATD were high versus non-ZZ, whether they were receiving augmentation therapy or not. | |||
| Piitulainen, 2003 [104] | Sweden | 5 | 2002 | Annual direct cost associated with AAT therapy Tailored dose: SEK 1 560 400 Standard dose: SEK 2 600 000 | NR | Tailored pharmacokinetic dosing of human AAT reduces the total annual dose and cost of i.v. AAT therapy. |
| Stoller, 2000 [116] | USA | 712 | 1997–1999 | NR | Resource 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] | USA | 1258 | 2011–2017 | After 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-diagnosis | Healthcare 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] | USA | 8881 | 2000–2017 | Adjusted 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, respectively | AATD 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, respectively | 12 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] | USA | 6832 | 2010–2015 | The introduction of a DMP was estimated to decrease costs of the management of patients with AATD by USD 13.5 million over 5 years | The savings attributed to the programme were due to 2555 exacerbations, 5180 ER visits, 9342 specialist visits and 105 358 GP visits avoided | A 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] | France | 365 | 2014–2017 | Mean 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] | USA | 2002–2014 | In 2014, hospitalisation costs adjusted to 2020 dollars for AATD was USD 108 million relative to all annual NIS discharges | AATD 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] | USA | 1872 AATD-related cirrhosis, 7488 non-AATD-related cirrhosis | 2011–2017 | Hospitalisation 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.