A new study presented at the 2013 American Thoracic Society International Conference suggests that using Alpha-1 proteinase inhibitor (A1-PI) to treat patients with Alpha-1 antitrypsin deficiency (AATD) can help slow down the progression of emphysema. The study showed the efficacy of A1-PIin preventing the loss of lung tissue as measured by computed tomography (CT) scan lung density at full inspiration (TLC), which is a more sensitive measure of disease progression than conventional parameters.This is the first prospective study to demonstrate the efficacy and safety of augmentation therapy in a randomized, placebo-controlled trial using this parameter.
"Our experience of the last quarter century has been that augmentation therapy is associated with better preserved lung function and reduced mortality, " said lead author Kenneth R. Chapman, M.D., director of the Asthma and Airway Centre of the University Health Network, in Toronto. "This randomized, placebo-controlled trial using a sensitive measure of lung density adds the most rigorous evidence to date that augmentation therapy slows the progression of emphysema in patients with Alpha-1 antitrypsin deficiency. The effect of A1-PI seen in this trial was both clinically and statistically significant, finally confirming its benefit in preventing the loss of lung tissue in patients with this potentially debilitating disease."
Chapman added that preliminary data from an extension trial suggest that early treatment with A1-PIshows persistent efficacy in patients with AATD and emphysema. In both the A1-PI and placebo groups who elected to continue treatment withA1-PI 60 mg/kg weekly, the benefit in CT scan lung density decline continued.
AATD is a hereditary condition that can severely affect a patient's lung function. The condition is marked by a low level or absence of A1-PI, a natural protein that protects the lung from breakdown by inhibiting neutrophil elastase, and protects lung elasticity. AATD can lead to emphysema at a young age (<45 years of age), especially among smokers, and progressive loss of lung function that can significantly impact everyday life and life expectancy.
There is no cure for AATD, but there are treatments for the symptoms of the disease, including bronchodilators and inhaled steroids, which help open the airways. Augmentation therapy, which is administered intravenously, has been shown to slow or halt the destruction of lung tissue in AATD.
The current trial, the largest clinical trial of this treatment to date, was a randomized, placebo-controlled, double-blind, multinational, multicenter phase III/IV study comparing the efficacy and safety ofA1-PIwith placebo in 180 subjects with emphysema due to AATD. Patients received A1-PIintravenously 60 mg/kg weekly or matching placebo over two years. The effect ofA1-PI on the progression of emphysema, the primary endpoint of the study, was assessed by the decline of lung density, measured by CT scan. Key secondary endpoints included changes in exercise capacity, symptoms score and rate of pulmonary exacerbations over two years.
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