Augmentation treatment for α1 antitrypsin deficiency may slow the progression of emphysema, a study in the Lancet shows.

Findings from observational and cohort studies had shown that the rate of FEV1 loss was slower in individuals with α1 antitrypsin deficiency who received α1 proteinase inhibitor (A1PI) augmentation treatment compared to those who did not.

But until now, its efficacy had not been substantiated by a randomised, placebo-controlled trial, the researchers noted in background information to their paper.

“CT-measured lung density is a more sensitive measure of disease progression in α1 antitrypsin deficiency emphysema than spirometry is, so we aimed to assess the efficacy of augmentation treatment with this measure,” they wrote.

In the two-year multi-centre RAPID trial the researchers randomly assigned 153 patients with α1 antitrypsin deficiency to α1 antitrypsin augmentation treatment (60 mg/kg) or placebo.

Patients had α1 antitrypsin serum concentrations of less than the 11 μM threshold for risk of emphysema and mild to moderate airflow obstruction (forced expired volume in 1 s 35–70% predicted).

Quantitative chest CT showed that the annual rate of lung density loss (a direct measure of the extent of emphysema) was significantly lower in the treated patients assessed over 2 years when measured at total lung capacity alone (–1·45 g/L per year vs –2·19 g/L per year; difference 0·74 g/L per year [95% CI 0·06–1·42]).

The finding could not be substantiated by lung density measurement at FRC alone or by the two measurements combined, noted the research team that included Jonathan Burdon from St Vincent’s Hospital in Melbourne.

Writing in an accompanying editorial Dr Ronald Crystal from the Department of Genetic Medicine, Weill Cornell Medical College, New York, said that with evidence of clinical efficacy now shown, use of augmentation treatment earlier than at present, before onset of decline in lung function, should be explored.

Diagnosis of α1 antitrypsin deficiency is a single blood test, and the data would suggest that treatment could begin earlier and lung parenchymal destruction could be prevented, he said.

However the challenge remained on finding a way to augment α1 antitrypsin concentrations in patients with α1 antitrypsin deficiency without the need for intravenous infusions every week, and to do so in a less costly manner (present treatment costs US$ 100000 per individual per year).

“We and others are therefore exploring gene therapy strategies to augment α1 antitrypsin concentrations using adeno-associated viral gene transfer vectors, a treatment that can potentially replace α1 antitrypsin augmentation with a single administration,” he said.

The study was funded by CSL Behring.