What is the management and treatment for Alpha 1 (A1AT) anti-trypsin deficiency?

From the Guidelines

The management of Alpha-1 Antitrypsin Deficiency (A1AT) focuses on preventing lung damage and treating existing symptoms, with augmentation therapy being conditionally recommended for patients with COPD and documented A1AT deficiency to preserve CT scan lung density and reduce mortality, as supported by high-quality evidence from the Canadian Thoracic Society meta-analysis and clinical practice guideline 1. The cornerstone treatment for patients with emphysema due to A1AT deficiency is augmentation therapy with intravenous alpha-1 proteinase inhibitor (also called alpha-1 antitrypsin), typically given at 60 mg/kg body weight weekly.

• Common brand names include Prolastin-C, Aralast, Zemaira, and Glassia.
• This therapy aims to raise serum levels above the protective threshold of 11 μmol/L (or 57 mg/dL) to slow lung destruction. Additional management includes standard COPD treatments:
• Bronchodilators (such as albuterol, tiotropium)
• Inhaled corticosteroids for exacerbations
• Pulmonary rehabilitation
• Supplemental oxygen if needed
• Vaccinations against influenza and pneumococcal disease Lifestyle modifications are crucial, with complete smoking cessation being imperative as smoking accelerates lung damage.
• Patients should avoid occupational respiratory irritants and air pollution. Liver disease management, when present, involves:
• Monitoring liver function
• Avoiding alcohol
• Potentially liver transplantation in severe cases Genetic counseling is recommended for family planning. Regular monitoring with pulmonary function tests every 6-12 months and liver function tests helps track disease progression and treatment effectiveness. The therapy works by restoring the protease-antiprotease balance in the lungs, preventing neutrophil elastase from destroying lung tissue unchecked, as supported by previous studies 1. Recent guidelines also emphasize the importance of targeted testing and genetic counseling for individuals with moderate and high clinical suspicion of A1AT deficiency, as well as the need for further research to address evidence gaps in the diagnosis and management of A1AT deficiency 1.

From the FDA Drug Label

Augmenting the levels of functional Alpha1-proteinase inhibitor by intravenous infusion is an approach to therapy for patients with Alpha1-PI deficiency. However, the efficacy of augmentation therapy in affecting the progression of emphysema has not been demonstrated in randomized, controlled clinical trials The intended theoretical goal is to provide protection to the lower respiratory tract by correcting the imbalance between neutrophil elastase and protease inhibitors. Augmentation therapy with Alpha1-Proteinase Inhibitor (Human) is indicated only in patients with severe congenital Alpha1-PI deficiency who have clinically evident emphysema

The management and treatment for Alpha 1 (A1AT) anti-trypsin deficiency involves augmentation therapy with Alpha1-Proteinase Inhibitor (Human) to increase the levels of functional Alpha1-proteinase inhibitor in the blood and lungs. This approach is intended to correct the imbalance between neutrophil elastase and protease inhibitors, providing protection to the lower respiratory tract. However, the efficacy of augmentation therapy in affecting the progression of emphysema has not been demonstrated in randomized, controlled clinical trials. Indications for augmentation therapy are limited to patients with severe congenital Alpha1-PI deficiency who have clinically evident emphysema 2.

From the Research

Management and Treatment of Alpha 1 Antitrypsin Deficiency

The management and treatment of Alpha 1 Antitrypsin (A1AT) deficiency involve a range of approaches, including:

• Augmentation therapy with purified A1AT preparations obtained through pooled human plasma to improve survival and disease-related quality of life, as well as slow down the progression of organ damage 3
• Weekly intravenous administration of purified AAT to treat loss-of-function lung disease 4
• Recombinant modified AAT and oral protease inhibitors, which are currently in clinical trials 4
• Small interfering RNA fazirsiran, which efficiently suppresses AAT production and is currently in phase 3 clinical trial, as a potential treatment for AATD-associated liver disease 4
• Genetic approaches, such as RNA editing, which are at earlier stages of development 4

Diagnosis and Screening

Diagnosis of A1AT deficiency is crucial for early intervention and management. The key to successful diagnosis is:

• Measuring serum AAT levels 5
• Determining the phenotype or genotype if low concentrations are found 5
• Using noninvasive tools for disease stratification and monitoring, such as cross-sectional and longitudinal data 4

Clinical Manifestations and Risk Factors

A1AT deficiency can lead to a range of clinical manifestations, including:

• Lung disease, such as chronic obstructive pulmonary disease (COPD) and emphysema 6, 7, 3
• Liver disease, such as liver cirrhosis and hepatocellular carcinoma (HCC) 4, 7, 3
• Other inflammatory, autoimmune, and neoplastic diseases 5 Risk factors that can affect disease progression include:
• Cigarette smoking or poor ventilation conditions 7
• Comorbidities or other risk factors, such as the heterozygous form (Pi*MZ) of AATD 4