Augmentation therapy is the only specific treatment for alpha1-antitrypsin (AAT) deficiency
Intravenous infusion of AAT, also known as augmentation therapy, is the only specific treatment available for AAT deficiency.1
Augmentation therapy has been demonstrated to raise levels of alpha1 antitrypsin in the blood and lungs above the threshold needed to protect lung tissue.2,3
- The goal of augmentation therapy is to correct the deficiency state and keep neutrophil elastase in check2,4
Serum levels of AAT during long-term therapy
The American Thoracic Society/European Respiratory Society guidelines and the COPD Foundation Clinical Practice Guidelines recommend intravenous augmentation therapy for AAT deficiency*,3,5
The evidence for augmentation therapy
The largest and longest cohort of AAT deficiency patients showed that survival was significantly increased with augmentation therapy.6
Cumulative 5-year mortality for patients with baseline FEV1 <50% predicted
Subjects were enrolled in a NHLBI Registry and included those with AAT serum levels below 11 μM (n=1026) or the PiZZ genotype (n=103). The objective was to study the decline of FEV1 and mortality in relation to augmentation therapy and other factors, including smoking status. Patients partially on augmentation therapy received it for 66% of the total period; most discontinuations (59%) were attributed to receiving a lung transplant.
Augmentation therapy resulted in a significant reduction in the rate of emphysema progression7
Integrated analysis: emphysema progression for augmentation therapy vs placebo
Integrated results from two randomised, placebo-controlled trials with a similar design and duration with 119 patients, 60 of whom were treated with augmentation therapy. The duration of the study was 2.5 years. FEV1 entry criterion for the first study was 30-80% of predicted, and treatment was 250 mg/kg body weight every 4 weeks. In the second, FEV1 entry criterion was 25-80% of predicted and treatment with 60 mg/kg body weight weekly. The loss of lung tissue and effect of augmentation therapy in alpha-1 subjects was measured with CT densitometry.
AAT: alpha1 antitrypsin; CI: confidence interval; COPD: chronic obstructive pulmonary disease; CT: computed tomography; FEV1: forced expiratory volume in 1 second; NHLBI: National Heart, Lung and Blood Institute; PD15: change in 15th percentile of lung density.
*Recommended for individuals with FEV1 35-60% of predicted.
References
- Miravitlles M, Dirksen A, Ferrarotti I, et al. European Respiratory Society statement: diagnosis and treatment of pulmonary disease in α1-antitrypsin deficiency. European Respiratory Journal. 2017;50(5).
- Wewers MD, Casolaro MA, Sellers SE, et al. Replacement therapy for alpha 1-antitrypsin deficiency associated with emphysema. N Engl J Med. 1987;316(17):1055-62.
- ATS, ERS. American Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency. Am J Respir Crit Care Med. 2003;168(7):818-900.
- Stoller JK, Aboussouan LS. Alpha1-antitrypsin deficiency. Lancet. 2005;365(9478):2225-36.
- Sandhaus RA, Turino G, Brantly ML, et al. The diagnosis and management of alpha-1 antitrypsin deficiency in the adult (Clinical Practice Guidelines). Chronic Obstr Pulm Dis (Miami). 2016;3(3):668-82.
- The Alpha-1-Antitrypsin Deficiency Registry Study Group. Survival and FEV1 decline in individuals with severe deficiency of alpha1-antitrypsin. Am J Respir Crit Care Med. 1998;158(1):49-59.
- Stockley RA, Parr DG, Piitulainen E, et al. Therapeutic efficacy of alpha-1 antitrypsin augmentation therapy on the loss of lung tissue: an integrated analysis of 2 randomised clinical trials using computed tomography densitometry. Respir Res. 2010;11:136.
A short-term study was performed to evaluate safety and dosing of alpha1 antitrypsin to maintain serum levels above 80 mg/dL. 21 patients with the PiZZ genotype were given 60 mg of active, plasma-derived, alpha1 antitrypsin per kg of body weight for 6 months.