From the Guidelines
In Europe, alpha-1 antitrypsin (AAT) replacement therapy is generally provided earlier than in the United States, often before emphysema develops, as supported by the American Thoracic Society/European Respiratory Society statement 1. The primary goal of AAT replacement therapy is to slow the progression of lung damage by restoring protective levels of this important protease inhibitor.
- The standard treatment involves weekly intravenous infusions of purified human AAT at a dose of 60 mg/kg, as shown to be biologically effective in increasing lung levels of AAT in AAT-deficient individuals 1.
- European guidelines typically recommend initiating AAT replacement therapy for patients with severe AAT deficiency (serum levels <11 μmol/L or approximately 50-80 mg/dL) who have declining lung function, even without established emphysema.
- In contrast, US guidelines usually require evidence of emphysema or other pulmonary disease before starting therapy, highlighting the difference in approach between the two regions. The rationale behind the European approach is that early intervention may slow the progression of lung damage by restoring protective levels of this important protease inhibitor, potentially preserving lung function before irreversible structural damage occurs, as suggested by observational studies such as the German–Danish study and the NHLBI Registry 1.
- These studies suggest that progression of emphysema may be slowed in patients with moderate emphysema (FEV1 31–65% predicted), and mortality may be decreased in patients with a lower FEV1.
- AAT deficiency causes lung damage through unopposed neutrophil elastase activity that destroys lung tissue, and earlier replacement aims to prevent this destructive process rather than treating established disease.
From the Research
Alpha 1 Antitrypsin Replacement Therapy in Europe and the United States
- The availability and timing of alpha 1 antitrypsin replacement therapy in Europe compared to the United States are not explicitly stated in the provided studies 2, 3, 4, 5, 6.
- However, it is mentioned that intravenous infusion of alpha-1 antitrypsin was approved by the United States Food and Drug Administration (FDA) in 1987 to treat emphysema associated with alpha-1 antitrypsin deficiency (AATD) 5.
- The studies suggest that alpha-1 antitrypsin replacement therapy is typically considered for individuals with severe forms of AATD, and its effectiveness in treating less severe forms is still being researched 2, 4, 5.
- There is no direct comparison between Europe and the United States regarding the timing of alpha 1 antitrypsin replacement therapy provision in the provided studies.
Timing of Alpha 1 Antitrypsin Replacement Therapy
- One study suggests that therapy should ideally be started earlier than normally envisaged and before the onset of clinical emphysema 4.
- Another study mentions that alpha-1 antitrypsin replacement therapy has proven clinical efficacy in slowing the decline of lung function associated with AATD progression, but it is only recommended for individuals with the most severe forms of AATD 5.
- The optimal timing of alpha 1 antitrypsin replacement therapy is still a topic of research, and more studies are needed to determine the best approach 2, 3, 4, 5, 6.
Research and Emerging Treatment Strategies
- There is currently extensive research into AATD and its treatment, with new therapeutic technologies being investigated, such as gene repair and other interference strategies, as well as the use of chemical chaperones 5.
- New sources of alpha-1 antitrypsin are also being investigated to ensure there are enough supplies to meet future demand, and new methods of assessing response to treatment are being evaluated 5.
- The COVID-19 pandemic has prompted physicians to develop additional strategies for delivering alpha-1 antitrypsin therapy, including self-administration, which can improve independence and well-being for patients with AATD 6.