No benefit found for acetylcysteine in IPF
SAN DIEGO - At 60 weeks, there was no significant difference in the change in FVC between 133 patients randomized to acetylcysteine 600 mg three times daily and 131 randomized to placebo (–0.18 L and –0.19 L, respectively; P = .77). There were no significant differences between the acetylcysteine group and the placebo group in rates of death (4.9% vs. 2.5%, respectively; P =.30) or acute exacerbations (2.3% in each group; P greater than .99) (N. Eng. J. Med. 2014 May 18 [doi: 10.1056/NEJMoa1401739]).
“Our results are applicable only to patients with idiopathic pulmonary fibrosis [IPF] who met the inclusion and exclusion criteria of this trial, and not to patients with more advanced disease or other forms of idiopathic interstitial pneumonia or interstitial lung disease,” said the researchers, all members of the Idiopathic Pulmonary Fibrosis Clinical Research Network and led by Dr. Ganesh Raghu, FCCP, director of the interstitial lung disease/sarcoid/pulmonary fibrosis program at the University of Washington, Seattle.
The study originally included a third arm in which patients received prednisone, azathioprine, and acetylcysteine, but it was halted after the data and safety monitoring board saw an increased risk of hospitalization and death, which led to a National Institutes of Health warning against use of the combination for IPF.
Overall, cardiac problems were more common in the acetylcysteine group than in the placebo patients (6.8% vs. 1.5%; P = .03), but gastrointestinal disorders were less common (0% vs. 4.6%; P = .01). There were trends favoring acetylcysteine in 6-minute walk distance and quality of life measures. Patients in the acetylcysteine group reported having better mental well-being.
Baseline characteristics were well matched in the two groups. Mean age was 67 years; 22% were women; 96% were white. Mean baseline FVC was 73% of the predicted value, and mean carbon monoxide diffusing capacity was 45% of the predicted value. Mean distance on the 6-minute walk test was 373 m.
At 60 weeks, 90.4% of the acetylcysteine group and 94.4% of the placebo group reported taking more than 80% of the recommended doses of the study drug.
“It is reasonable to shift our understanding of the pathogenesis of this disease,” Dr. Gary M. Hunninghake, director of the sarcoidosis and granulomatous lung disease service at Brigham and Women’s Hospital, Boston, wrote in an editorial (N. Eng. J. Med. 2014 May 18 [doi: 10.1056/NEJMe1403448]). IPF “is a disease perpetuated by aberrant wound healing, rather than primarily by chronic inflammation. With new understanding comes new hope.”