From the Guidelines
In Australia, alpha-1 antitrypsin (AAT) replacement therapy is provided under similar clinical circumstances as in the United States, with both countries generally not providing it before the development of emphysema. The Australian government funds AAT replacement therapy through the Life Saving Drugs Program for patients who have severe AAT deficiency (serum levels <11 μmol/L) and established emphysema with moderate airflow obstruction (FEV1 between 30-65% predicted) 1. This approach mirrors the US practice where therapy is typically initiated after emphysema diagnosis. The standard treatment involves weekly intravenous infusions of purified human AAT at a dose of 60 mg/kg, as supported by earlier studies 1. Key considerations for initiating therapy include:
- Severe AAT deficiency
- Established emphysema
- Moderate airflow obstruction
- Abstinence from smoking, as smoking accelerates lung damage and reduces the effectiveness of replacement therapy. The rationale behind waiting for emphysema development is based on cost-effectiveness considerations and the preventative rather than restorative nature of the therapy - it can slow progression but cannot reverse existing lung damage, as noted in observational studies suggesting a reduction in spirometric progression in alpha-1 antitrypsin deficiency patients treated with augmentation therapy versus patients who are not treated 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Alpha 1 Antitrypsin Replacement Therapy
- The provided studies do not specifically compare the timing of alpha 1 antitrypsin replacement therapy in Australia versus the United States 2, 3, 4, 5, 6.
- However, it is mentioned that in the United States, alpha 1 antitrypsin replacement therapy is only approved for individuals with the most severe forms of alpha 1 antitrypsin deficiency (AATD) and is not recommended for those with less severe forms or wild-type heterozygotes 5.
- The studies suggest that alpha 1 antitrypsin replacement therapy can slow the progression of emphysema in individuals with AATD, but the timing of treatment initiation is not explicitly compared between countries 2, 3, 4, 5.
- There is ongoing research into new therapeutic strategies for AATD, including gene therapy and alternative sources of alpha 1 antitrypsin, which may potentially lead to earlier treatment initiation in the future 4, 5.
Emphysema Treatment
- Emphysema is a chronic obstructive pulmonary disease (COPD) phenotype characterized by destruction of lung parenchyma, and alpha 1 antitrypsin deficiency is a genetic cause of emphysema 6.
- The studies highlight the importance of acknowledging non-alpha 1 antitrypsin deficiency emphysema as a clinical diagnosis and propose targeting decelerating proteolysis and restoring damage as main therapeutic goals 6.
- Current pharmacological treatments for emphysema have less favorable effects in emphysematous than in non-emphysematous COPD patients, and new therapeutic candidates such as vitamin A/K, hyaluronan, copper, and roflumilast are being investigated 6.