title: α1-Proteinase inhibitor (human) in the treatment of hereditary emphysema secondary to α1-antitrypsin deficiency: number and costs of years of life gained.
abstract: BACKGROUND
  α(1)-Antitrypsin deficiency (α-ATD) is a disorder inherited in an autosomal recessive pattern, with co-dominant alleles known as the protease inhibitor system (Pi). The main function of α(1)-antitrypsin (α-AT) is to protect the lungs against a powerful elastase released from neutrophil leucocytes. α-ATD typically presents with a serum α-AT level of <50 mg/dL. In severe α-ATD, phenotype PiZZ, protection of the lungs is compromised, leading to an accelerated decline in forced expiratory volume in 1 second (FEV(1)). As a result, a patient may develop pulmonary emphysema of the panacinar type at a young age (third to fourth decades of life), with cigarette smoking being the most significant additional risk factor. It has been shown that weekly or monthly infusion of human α-AT is effective in raising serum α-AT levels to desired levels (>80 mg/dL), with few, if any, adverse effects.
  
  
  OBJECTIVE
  The present study was designed to discern the number of years of life gained, and the expense per year of life gained, associated with use of α-AT augmentation therapy (α(1)-proteinase inhibitor [human]), relative to 'no therapeutic intervention' in persons with α-ATD.
  
  
  METHODS
  Monte Carlo simulation (MCS) was used to: (i) estimate the number of years of life gained; and (ii) estimate the health service expenditures per year of life gained for persons receiving, or not receiving, α-AT augmentation therapy. MCS afforded a decision-analytical framework parameterized with both stochastic (random) and deterministic (fixed) components, and yielded a fiscal risk-profile for each simulated cohort of interest (eight total: by sex, smoking status [non-smoker; or past use (smoker)]; and use of α-AT augmentation therapy). The stochastic components employed in the present inquiry were: (i) age-specific body weight, and height; (ii) age-specific mortality; and (iii) the probability distribution for receipt of a lung transplant, as a function of FEV(1). The deterministic components employed in the present inquiry were: (i) age in years for the simulated cohort; (ii) outlays for α-AT augmentation therapy; (iii) health service expenditures associated with receipt of a lung transplant; (iv) annual decline in FEV(1); (v) percent predicted FEV(1); (vi) initiation of α-AT augmentation therapy as a function of percent predicted FEV(1); (vii) need for a lung transplant as a function of percent predicted FEV(1); (viii) annual rate of lung infection; and (ix) mortality as a function of percent predicted FEV(1). Results are reported from a payer perspective ($US, year of costing 2010).
  
  
  RESULTS
  Receipt of α-AT augmentation therapy was associated with a significant increase (p < 0.05) in years of life gained, with female smokers gaining an estimated mean 7.14 years (cost per year: $US248 361 [95% CI 104 531, 392 190]); female non-smokers gained an estimated mean 9.19 years (cost per year: $US160 502 [95% CI 37 056, 283 947)]); male smokers gained an estimated mean 5.93 years (cost per year: $US142 250 [95% CI 48 467, 236 032]); and male non-smokers gained an estimated mean 10.60 years (cost per year: $US59 234 [95% CI 20 719, 97 548]).
  
  
  CONCLUSIONS
  Use of α-AT augmentation therapy was associated with an increase in years of life gained by sex and history of tobacco use, and at a cost per year of life gained comparable to that of other evidenced-based interventions.
authors.affiliation: Pharmacoeconomics and Pharmacoepidemiology Research Unit, Washington State University, Spokane, WA, USA. sclar@mail.wsu.edu
authors.forename: David Alexander
authors.initials: DA
authors.lastname: Sclar
authors.forename: Marc A
authors.initials: MA
authors.lastname: Evans
authors.forename: Linda M
authors.initials: LM
authors.lastname: Robison
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Skaer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017281:Cost of Illness; D003661:Decision Support Techniques; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008017:Life Expectancy; D008297:Male; D008875:Middle Aged; D009010:Monte Carlo Method; D011656:Pulmonary Emphysema / Q000188:drug therapy* / Q000191:economics / Q000209:etiology; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects*; D055815:Young Adult; D000515:alpha 1-Antitrypsin / Q000008:administration & dosage*; D019896:alpha 1-Antitrypsin Deficiency / Q000188:drug therapy* / Q000191:economics / Q000503:physiopathology
chemical_list: D000515:alpha 1-Antitrypsin