Study Finds Acetylcysteine Offers No Benefits for Patients with IPF

Previous studies have suggested that acetylcysteine is a beneficial treatment for idiopathic pulmonary fibrosis (IPF); however, data from placebo-controlled trials are lacking. A recent study by the Idiopathic Pulmonary Fibrosis Clinical Research Network examined the effects of acetylcysteine versus placebo for the treatment of IPF [N Engl J Med. 2014; DOI:10.1056/NEJMoa1401739].

The study was carried out at 25 clinical centers throughout the United States. The double-blind, placebo-controlled trial randomly included IPF patients with mild-to-moderate impairment in pulmonary function, which was defined as a forced vital capacity (FVC) of ≥50% of the predicted value and a carbon monoxide diffusing capacity of ≥30% of the predicted value. All patients were required to meet the modified criteria of the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Association for the diagnosis of IPF. Patients who were 35 to 85 years of age and who had received an IPF diagnosis within 48 months before enrollment were eligible for study inclusion.

Originally, study participants were to receive either a 3-drug regimen of prednisone, azathioprine, and acetylcysteine; acetylcysteine alone; or placebo. However, the study was interrupted due to safety concerns associated with the 3-drug regimen, though the trial continued with the 2 other groups (acetylcysteine vs placebo) without disturbance. Patients who were originally randomly assigned to the discontinued 3-drug group were not allowed to participate in the 2-group revised study. The original study period took place from December 2009 to mid-October 2011, and the revised study period took place from January 2012 to July 2012.

A total of 264 patients were included in the 2-group study—133 in the acetylcysteine group and 131 in the placebo group. The baseline characteristics of the patients in each study group were well matched, according to the authors. The mean participant age was 67 years, 22% of the patients were women, and 96% were white. The mean FVC was 73% of the predicted value, and the mean carbon monoxide diffusing capacity was 45% of the predicted value.

The primary outcome of the study was the change in FVC over a 60-week period. Some of the secondary outcomes included rate and time until death and frequency of acute exacerbations, among others.

At 60 weeks, the researchers found no significant difference in the change in FVS between the acetylcysteine group and the placebo group (-0.18 liters vs -0.19 liters, respectively; P=.77).

There were also no significant differences between the acetylcysteine and placebo groups in rates of death (4.9% [n=6 patients] vs 2.5% [n=3 patients], respectively; P=.30) or acute exacerbation (2.3% [n=3 patients] in each group; P>.99).

There were also no significant differences in terms of rates of serious adverse events, except for cardiac disorders, which occurred in 9 of 133 patients in the acetylcysteine group (6.8%) versus 2 in 131 patients in the place group (1.5%; P=.03).

The study’s researchers noted that these findings are only applicable to patients with IPF who meet the same inclusion and exclusion criteria of this trial. The findings are not generalizable to IPF patients with more advanced disease or other forms of idiopathic interstitial pneumonia or interstitial lung disease.

The researchers concluded that, despite previous reports that suggested acetylcysteine is beneficial for the treatment of IPF, this study did not find a significant benefit with respect to the preservation of FVC in patients with IPF with mild-to-moderate impairment in lung function.