What is the primary treatment for Alpha 1 antitrypsin deficiency?

Primary Treatment for Alpha-1 Antitrypsin Deficiency

Intravenous augmentation therapy is the primary treatment for Alpha-1 Antitrypsin Deficiency (AATD) in patients with documented emphysema, FEV1 <80% predicted, and severely reduced functional AAT levels (<11 μmol/L or <0.57 g/L). 1

Diagnosis and Patient Selection

Before initiating treatment, proper diagnosis is essential:

1. Testing criteria: Test for AATD in:

   • Patients with COPD, especially early-onset (<40 years)
   • Unexplained bronchiectasis
   • Adult-onset asthma with persistent airflow obstruction
   • Family history of AATD or COPD
   • Basilar pan-lobular emphysema 1, 2

2. Diagnostic approach:

   • Initial screening: Serum AAT level
   • If level <23 μmol/L (<1.2 g/L): Proceed to genetic testing with DNA sequencing of SERPINA1 gene
   • CT scan to document presence and extent of emphysema 1

Augmentation Therapy Criteria

Augmentation therapy is indicated for patients with:

• Documented SERPINA1 genotypes associated with AATD (typically Pi*ZZ)
• Severely reduced functional AAT level (<11 μmol/L or <0.57 g/L)
• FEV1 <80% predicted
• Documented emphysema on CT scan
• Non-smoking status (current or former)
• Receiving optimal pharmacological and non-pharmacological therapies for COPD 1, 2

Treatment Regimen

• Standard dosing: 60 mg/kg body weight administered intravenously weekly 1, 2
• Target level: Maintain serum AAT levels above the protective threshold (>15 μmol/L) 2
• Duration: Lifelong therapy, as AATD is a genetic condition requiring continuous treatment

Evidence of Efficacy

Augmentation therapy has demonstrated benefits in:

1. Slowing lung density decline:

   • High-quality evidence shows preservation of CT scan lung density 1
   • RAPID trial showed significant slowing of lung density decline over 2 years 1

2. Reducing FEV1 decline:

   • FEV1 decline of 53 ml/year in treated vs. 75 ml/year in untreated patients 1
   • Most beneficial in patients with moderate emphysema (FEV1 31-65% predicted) 1, 2

3. Reducing mortality:

   • Very low-quality evidence suggests reduced mortality 1
   • NHLBI Registry showed lower mortality rates in those receiving augmentation therapy (OR 0.79, p<0.02) 1

Monitoring and Follow-up

• Pulmonary function tests every 6-12 months
• CT scans to assess emphysema progression
• Monitor for adverse reactions to therapy 2

Safety Profile

• Generally well-tolerated
• Mild reactions include fever, chills, and dyspnea (reported in approximately 5% of patients)
• Rare anaphylactic reactions have been reported 1, 2

Important Considerations and Caveats

• Smoking cessation is mandatory before initiating augmentation therapy, as smoking significantly reduces efficacy 2
• Therapy is less beneficial in very advanced disease (FEV1 <30% predicted) 2
• Limited evidence exists for non-PiZZ genotypes (e.g., PiSZ, Pi*MZ) 3
• The therapy addresses only lung manifestations, not liver or skin manifestations of AATD 2
• Treatment should be initiated as early as possible once criteria are met to prevent irreversible lung damage 1

Comprehensive Management

Augmentation therapy should be part of a comprehensive management plan that includes:

• Inhaled bronchodilators
• Preventive vaccinations against influenza and pneumococcus
• Supplemental oxygen when indicated
• Pulmonary rehabilitation for individuals with functional impairment
• Consideration of lung transplantation for selected individuals with severe functional impairment 1