PMID- 22480280
OWN - NLM
STAT- MEDLINE
DCOM- 20120810
LR  - 20211021
IS  - 1179-1918 (Electronic)
IS  - 1173-2563 (Linking)
VI  - 32
IP  - 5
DP  - 2012 May 1
TI  - alpha1-Proteinase inhibitor (human) in the treatment of hereditary emphysema 
      secondary to alpha1-antitrypsin deficiency: number and costs of years of life gained.
PG  - 353-60
LID - 10.2165/11631920-000000000-00000 [doi]
AB  - BACKGROUND: alpha(1)-Antitrypsin deficiency (alpha-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 alpha(1)-antitrypsin (alpha-AT) is to protect 
      the lungs against a powerful elastase released from neutrophil leucocytes. alpha-ATD 
      typically presents with a serum alpha-AT level of <50 mg/dL. In severe alpha-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 alpha-AT is effective in raising serum alpha-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 alpha-AT augmentation therapy (alpha(1)-proteinase 
      inhibitor [human]), relative to 'no therapeutic intervention' in persons with 
      alpha-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, alpha-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 alpha-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 alpha-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 alpha-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 alpha-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]). 
      CONCLUSION: Use of alpha-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.
FAU - Sclar, David Alexander
AU  - Sclar DA
AD  - Pharmacoeconomics and Pharmacoepidemiology Research Unit, Washington State 
      University, Spokane, WA, USA. sclar@mail.wsu.edu
FAU - Evans, Marc A
AU  - Evans MA
FAU - Robison, Linda M
AU  - Robison LM
FAU - Skaer, Tracy L
AU  - Skaer TL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - New Zealand
TA  - Clin Drug Investig
JT  - Clinical drug investigation
JID - 9504817
RN  - 0 (alpha 1-Antitrypsin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Cost of Illness
MH  - Decision Support Techniques
MH  - Female
MH  - Forced Expiratory Volume
MH  - Humans
MH  - Life Expectancy
MH  - Male
MH  - Middle Aged
MH  - Monte Carlo Method
MH  - Pulmonary Emphysema/*drug therapy/economics/etiology
MH  - Risk Factors
MH  - Sex Factors
MH  - Smoking/*adverse effects
MH  - Young Adult
MH  - alpha 1-Antitrypsin/*administration & dosage
MH  - alpha 1-Antitrypsin Deficiency/*drug therapy/economics/physiopathology
EDAT- 2012/04/07 06:00
MHDA- 2012/08/11 06:00
CRDT- 2012/04/07 06:00
PHST- 2012/04/07 06:00 [entrez]
PHST- 2012/04/07 06:00 [pubmed]
PHST- 2012/08/11 06:00 [medline]
AID - 10.2165/11631920-000000000-00000 [doi]
PST - ppublish
SO  - Clin Drug Investig. 2012 May 1;32(5):353-60. doi: 
      10.2165/11631920-000000000-00000.