What is the management for a patient with PI (Protease Inhibitor) alpha 1 AT (Alpha-1 Antitrypsin) deficiency?

From the Guidelines

Management of PI alpha 1 AT deficiency should prioritize augmentation therapy with intravenous alpha-1 proteinase inhibitor, as well as standard COPD management and liver disease prevention, to improve quality of life and reduce morbidity and mortality. The management approach should be based on the most recent and highest quality evidence, which suggests that augmentation therapy can reduce mortality and slow disease progression in patients with moderately advanced emphysema due to severe alpha-1 antitrypsin deficiency 1. Key components of management include:

• Augmentation therapy with intravenous alpha-1 proteinase inhibitor (Prolastin, Aralast, Zemaira, or Glassia) at 60 mg/kg weekly to maintain protective serum levels above 11 μmol/L, as recommended for patients with AAT levels below 11 μmol/L and FEV1 between 30-65% predicted 1
• Standard COPD management, including bronchodilators, inhaled corticosteroids, pulmonary rehabilitation, and oxygen therapy when indicated
• Smoking cessation, as smoking accelerates lung destruction
• Vaccinations against influenza, pneumococcus, and COVID-19 to prevent respiratory infections
• Liver disease management, including avoiding alcohol, hepatotoxic medications, and regular monitoring with liver function tests and ultrasound, with severe cases potentially requiring liver transplantation
• Genetic counseling for patients and their families This comprehensive approach addresses both the underlying protein deficiency and manages the pulmonary and hepatic manifestations of the disease, potentially slowing disease progression and improving quality of life 1.

From the FDA Drug Label

1 INDICATIONS AND USAGE

GLASSIA is an Alpha1-Proteinase Inhibitor (Human), indicated for chronic augmentation and maintenance therapy in individuals with clinically evident emphysema due to severe hereditary deficiency of Alpha1-PI, also known as alpha1-antitrypsin (AAT) deficiency

12 CLINICAL PHARMACOLOGY

1. 1 Mechanism of Action GLASSIA administration is intended to inhibit serine proteases such as neutrophil elastase (NE), which is capable of degrading protein components of the alveolar walls and which is chronically present in the lung. Alpha1-PI deficiency is a chronic, autosomal, co-dominant hereditary disorder characterized by reduced levels of Alpha1-PI in the blood and lungs

Augmenting the levels of functional protease inhibitor by intravenous infusion is an approach to therapy for patients with Alpha1-PI deficiency.

The management for a patient with PI alpha 1 AT deficiency involves chronic augmentation and maintenance therapy with Alpha1-Proteinase Inhibitor (Human), such as GLASSIA, to inhibit serine proteases and provide protection to the lower respiratory tract. The goal is to correct 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, 2.

Key points:

• GLASSIA is indicated for individuals with clinically evident emphysema due to severe hereditary deficiency of Alpha1-PI.
• The clinical benefit of increased blood levels of Alpha1-PI at the recommended dose has not been established.
• Augmentation therapy is intended to provide protection to the lower respiratory tract by correcting the imbalance between neutrophil elastase and protease inhibitors.

From the Research

Management of PI Alpha 1 AT Deficiency

The management of patients with PI (Protease Inhibitor) alpha 1 AT (Alpha-1 Antitrypsin) deficiency involves several strategies, including:

• Augmentation therapy, which is the only approved pharmacological therapy that can delay the progression of emphysema 3, 4, 5, 6
• Monitoring and managing lung and liver disease, which may involve lung function tests, computed tomography (CT) densitometry, and biological markers 4, 6
• Identifying and managing risk factors, such as smoking and alcohol use, which can exacerbate lung and liver disease 4, 7
• Considering alternative strategies, such as gene therapy, induced pluripotent stem cells, and prevention of AAT polymerization inside hepatocytes, which are currently being investigated 3, 5, 7

Diagnosis and Screening

Diagnosis and screening for alpha-1 antitrypsin deficiency are crucial for early detection and management, and may involve:

• Testing for AATD in all adults with symptomatic fixed airflow obstruction, whether clinically labeled as COPD or asthma 6
• Testing for AATD in individuals with unexplained bronchiectasis or liver disease 6
• Family testing of first-degree relatives, which is currently the most efficient detection technique 6

Treatment Options

Treatment options for alpha-1 antitrypsin deficiency include:

• Intravenous augmentation therapy with purified pooled human plasma-derived alpha-1 antitrypsin, which is available in many European countries and has been shown to reduce the progression of emphysema in PiZZ patients 4, 6
• Lung volume reduction or transplant, which may be considered in patients with severe lung disease 4
• Novel therapeutic approaches, such as gene therapy and induced pluripotent stem cells, which are currently being investigated 3, 5, 7