What is the management and treatment for alpha 1 antitrypsin deficiency?

From the Guidelines

The management of alpha-1 antitrypsin deficiency (AATD) should prioritize augmentation therapy with intravenous alpha-1 proteinase inhibitor, as it has been shown to preserve CT scan lung density and reduce mortality in patients with COPD and documented A1AT deficiency, as conditionally recommended by the Canadian Thoracic Society meta-analysis and clinical practice guideline 1. The goal of treatment is to prevent lung damage and manage existing symptoms.

• Augmentation therapy with intravenous alpha-1 proteinase inhibitor (such as Prolastin, Aralast, Zemaira, or Glassia) at 60 mg/kg weekly is the cornerstone treatment for patients with emphysema and severe deficiency (serum levels <11 μmol/L or 50-80 mg/dL) 1.
• Standard COPD treatments are also essential, including bronchodilators (both short and long-acting), inhaled corticosteroids for those with frequent exacerbations, pulmonary rehabilitation, and supplemental oxygen if hypoxemia is present.
• Lifestyle modifications are crucial: complete smoking cessation is imperative as smoking accelerates lung damage, and avoiding environmental pollutants and respiratory irritants is important.
• Vaccinations against influenza, pneumococcal disease, and COVID-19 help prevent respiratory infections.
• Prompt treatment of respiratory infections with antibiotics is necessary to minimize lung damage.
• For patients with advanced disease, lung transplantation may be considered.
• Liver disease management includes avoiding alcohol and hepatotoxic medications, with liver transplantation as an option for end-stage liver disease. The management of AATD requires a comprehensive approach because the deficiency leaves lung tissue vulnerable to destruction by neutrophil elastase, particularly in the lower lobes, leading to early-onset emphysema. Key patient characteristics that may benefit from augmentation therapy include:
• Never or previously smoked
• Have FEV1 < 80% predicted
• Have documented emphysema
• Have documented SERPINA1 genotypes associated with A1AT deficiency
• Have severely reduced functional A1AT level (<11 mmol/L or <0.57 g/L)
• Are receiving optimal pharmacological and non-pharmacological therapies for COPD 1.

From the FDA Drug Label

Augmentation therapy with Alpha1-Proteinase Inhibitor (Human) is indicated only in patients with severe congenital Alpha1-PI deficiency who have clinically evident emphysema Augmenting the levels of functional Alpha1-proteinase inhibitor by intravenous infusion is an approach to therapy for patients with Alpha1-PI deficiency. The intended theoretical goal is to provide protection to the lower respiratory tract by correcting the imbalance between neutrophil elastase and protease inhibitors.

The management and treatment for alpha 1 antitrypsin deficiency involves augmentation therapy with Alpha1-Proteinase Inhibitor (Human) for patients with severe congenital Alpha1-PI deficiency who have clinically evident emphysema. The goal of this therapy is to provide protection to the lower respiratory tract by correcting the imbalance between neutrophil elastase and protease inhibitors. However, the efficacy of augmentation therapy in affecting the progression of emphysema has not been demonstrated in randomized, controlled clinical trials 2.

Key points:

• Augmentation therapy is indicated for patients with severe congenital Alpha1-PI deficiency and clinically evident emphysema.
• The therapy aims to correct the imbalance between neutrophil elastase and protease inhibitors.
• The clinical benefit of increased blood levels of Alpha1-PI at the recommended dose has not been established 2.
• The clinical efficacy of Alpha1-PI products in influencing the course of pulmonary emphysema or the frequency, duration, or severity of pulmonary exacerbations has not been demonstrated in randomized, controlled clinical trials 2.

From the Research

Management and Treatment of Alpha 1 Antitrypsin Deficiency

The management and treatment of alpha 1 antitrypsin deficiency (AATD) involve various approaches to slow the progression of the disease and manage its symptoms. Some key aspects of management and treatment include:

• Augmentation Therapy: Alpha 1 antitrypsin (AAT) augmentation is effective in slowing the progression of emphysema due to AAT deficiency (AATD) 3, 4, 5. This therapy involves weekly infusions of human plasma-derived, purified α1-antitrypsin.
• Lung Transplantation: Lung transplantation is the only treatment option available for patients with end-stage lung disease due to AATD 3. Survival rates for lung transplantation are significantly higher for patients with AATD-related chronic obstructive pulmonary disease (COPD) compared with non-AATD-related COPD.
• Liver Transplantation: Liver transplantation is the only treatment option available for patients with end-stage liver disease due to AATD 3, 6, 7. Survival rates for patients with AATD undergoing liver transplantation are also favorable.
• Combined Lung and Liver Transplantation: In severe cases, where patients have simultaneous end-stage lung and liver disease, combined lung and liver transplantation is a treatment option with favorable outcomes 3.
• Standard Therapies for COPD: Treatment of A1ATD-associated lung disease includes standard therapies that are also used for the treatment of COPD, in addition to augmentation therapy 7.

Key Considerations

Some key considerations in the management and treatment of AATD include:

• Early Diagnosis: Early diagnosis and subsequent prevention of lung inflammation due to cigarette smoking, infection, and airborne irritants form the most rational approach to slow the progression of the lung destruction associated with alpha 1AT deficiency 6.
• Genetic Mutation: New therapies that target the misfolded α1-antitrypsin or attempt to correct the underlying genetic mutation are currently under development 7.
• Underdiagnosis: A1ATD is frequently underdiagnosed or misdiagnosed as asthma, chronic obstructive pulmonary disease (COPD), or cryptogenic liver disease 7.