Should Health-Care Systems Pay for Replacement Therapy in Patients With Alpha1-Antitrypsin Deficiency? A Critical Review and Cost-Effectiveness Analysis

Stephan A. Alkins, MD and Patrick O'Malley, MD, MPH From the Pulmonary and Critical Care Medicine Service (Dr. Alkins) and the Department of Internal Medicine (Dr. O'Malley), Walter Reed Army Medical Center, Washington, DC.


CHEST. 2000;117(3) 

In This Article

Abstract and Introduction

Study objectives: Assess cost effectiveness for providing alpha1-antitrypsin (alpha1-AT) replacement therapy to individuals with severe COPD and alpha1-AT deficiency.
Materials and methods: The electronic databases MEDLINE and EMBASE were searched, and relevant bibliographies were reviewed. Effect size, defined as the absolute risk difference between treated and untreated groups, was taken from the highest level of supporting evidence. The cost for providing alpha1-AT replacement therapy was analyzed from a payer perspective and was based on Medicare reimbursement rates. Effect size and costs were varied. The year of life saved was discounted up to 7%.
Results: The incremental cost per year of life saved for alpha1-AT replacement therapy (60 mg/kg/wk IV) in a 70-kg subject with severe alpha1-AT deficiency and an FEV1 < 50% of predicted based on the National Institutes of Health (NIH) Registry mortality rate data is $13,971. The incremental cost depends substantially on the mortality rate reduction. When the effect size is altered from 10 to 70%, with the cost fixed at $52,000, the incremental cost per year of life saved ranges from $152,941 to $7,330. When effect size is 55% (as in the NIH Registry) but costs are increased almost 300%, from $52,000 to $150,000 per year, then the incremental cost per year of life saved increases from $13,971 to $40,301.
Conclusion: No randomized, placebo-controlled trials are available to assess mortality rate reduction with alpha1-AT replacement therapy. The best currently available data are observational, from the NIH Registry. Based on these data, alpha1-AT replacement therapy is cost-effective in individuals who have severe alpha1-AT deficiency and severe COPD.

alpha1 -antitrypsin (alpha1-AT) is a serum protease inhibitor that protects against neutrophil elastase in the lower respiratory tract. alpha1-AT deficiency, first described by Laurell and Eriksson,[1] is associated with the development of premature emphysema that typically occurs in the third to fourth decades of life.[2] This autosomal codominant disorder is thought to be responsible for approximately 2% of all cases of emphysema in the United States.[3]

Replacement therapy with pooled human alpha1-AT is being used to treat subjects with alpha1-AT deficiency. While infusion of alpha1-AT is safe[4,5,6,7] and has been approved by the Food and Drug Administration for replacement therapy, the benefits of this therapy have never been definitively proven. Observational studies have suggested that in patients with at least moderate airway obstruction, replacement therapy impedes the decline in FEV1.[8,9,10]

Only one study has assessed the impact of replacement therapy on mortality.[10] In that study, the 5-year mortality rate in those subjects with an initial FEV1 < 50% ranged from 33% in the untreated to 15% in the treated group (p < 0.001).

The cost for providing augmentation therapy with human pooled alpha1-AT is expensive, approximately $52,000 per year for a 70-kg patient. While this therapy seems to abate the accelerated annual FEV1 decline and to improve the mortality rate, is it cost-effective? We analyzed the cost-effectiveness of this therapy from a payer perspective based on the best evidence available on replacement therapy in individuals with severe alpha1-AT deficiency.


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