From the Guidelines
Treatment for alpha-1 antitrypsin deficiency (AATD) primarily involves augmentation therapy with intravenous alpha-1 proteinase inhibitor (A1PI) for patients with severe deficiency (typically ZZ genotype) and evidence of emphysema, as supported by the most recent Canadian Thoracic Society meta-analysis and clinical practice guideline 1. The standard regimen is 60 mg/kg body weight administered weekly as an IV infusion, with the goal of raising and maintaining serum levels above the protective threshold of 11 μmol/L to slow the progression of emphysema. Some key points to consider in the management of AATD include:
- Augmentation therapy has been shown to slow the decline in lung density, as measured by CT scan, and may improve survival 1.
- The RAPID trial, a 2-year randomized controlled trial, demonstrated a significant slowing of lung density decline in patients receiving augmentation therapy compared to those receiving placebo 1.
- Beyond augmentation therapy, management of AATD includes standard treatments for COPD, such as:
- Bronchodilators (e.g. tiotropium, salmeterol, or formoterol)
- Inhaled corticosteroids for those with frequent exacerbations
- Pulmonary rehabilitation
- Supplemental oxygen if hypoxemic
- Vaccination against pneumococcal disease and influenza
- Lifestyle modifications are crucial, with smoking cessation being absolutely essential as smoking accelerates lung damage dramatically in these patients.
- Liver disease, another manifestation of AATD, is managed supportively with monitoring for complications, and severe cases may require liver transplantation.
- Lung transplantation remains an option for end-stage lung disease.
- Early diagnosis is important as treatment is most effective before significant lung damage occurs. It is worth noting that the Canadian Thoracic Society guidelines recommend that patients with severe AATD be managed with optimal pharmacological and nonpharmacological therapies, including smoking cessation, vaccinations, pulmonary rehabilitation, and comprehensive case management 1.
From the FDA Drug Label
Augmenting the levels of functional protease inhibitor by intravenous infusion is an approach to therapy for patients with Alpha1-PI deficiency. Administration of GLASSIA to patients with Alpha1-PI deficiency augments the level of the deficient protein.
- Treatment: The treatment for alpha one antitrypsin deficiency is augmentation therapy with Alpha1-Proteinase Inhibitor (Human), such as GLASSIA, which is intended to inhibit serine proteases like neutrophil elastase.
- Indication: GLASSIA is indicated for patients with severe Alpha1-PI deficiency who have clinically evident emphysema.
- Goal: The intended theoretical goal of augmentation therapy is to provide protection to the lower respiratory tract by correcting the imbalance between neutrophil elastase and protease inhibitors.
- Efficacy: However, the efficacy of augmentation therapy in affecting the progression of emphysema has not been demonstrated in randomized, controlled clinical trials 2.
From the Research
Treatment Options for Alpha-1 Antitrypsin Deficiency
- Augmentation therapy is a specific treatment for individuals with alpha-1 antitrypsin deficiency (AATD) who have developed pulmonary disease, as stated in 3, 4, 5.
- This therapy involves the intravenous infusion of purified human plasma-derived alpha-1 antitrypsin (AAT) to correct the A1AT deficiency state, as mentioned in 3, 4.
- There are six augmentation therapy preparations that have received FDA approval, all of which derive from pooled human plasma, as noted in 3.
Efficacy and Safety of Augmentation Therapy
- Augmentation therapy has been associated with effective elevations of A1AT levels and function in serum and lung epithelial fluid, as reported in 4.
- Observational studies suggest that augmentation therapy may lead to attenuation in lung function decline, particularly in patients with moderate impairment of lung function, as stated in 4.
- Augmentation therapy has a relative paucity of side effects, but it is highly expensive, as mentioned in 4.
Future Directions and Alternative Therapies
- Alternative strategies are being investigated, including the use of gene therapy or induced pluripotent stem cells, and non-augmentation strategies to prevent AAT polymerisation inside hepatocytes, as discussed in 6, 7.
- Recombinant alternatives to the plasma-derived protein, novel formulations, and novel administration routes are also being explored, as reported in 7.
- The optimal dose of augmentation therapy is being revised, as well as more individualized assessment of who needs this therapy, as noted in 5.