SAN DIEGO – Acetylcysteine does not preserve forced vital capacity in idiopathic pulmonary fibrosis patients with mild to moderate lung function impairment, according to a placebo-controlled trial published online May 18 in the New England Journal of Medicine and presented by Dr. Ganesh Raghu at an international conference of the American Thoracic Society.
At 60 weeks, there was no significant difference in the change in FVC between 133 patients who had been randomized to acetylcysteine 600 mg three times daily and 131 randomized to placebo (–0.18 L and –0.19 L, respectively; P = .77). There also were no significant differences between the acetylcysteine group and the placebo group in the 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]).
University of Washington
Dr. Ganesh Raghu
"It must be emphasized that our results are applicable only to patients with idiopathic pulmonary fibrosis 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 investigators, all members of the Idiopathic Pulmonary Fibrosis Clinical Research Network and led by Dr. Raghu, 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. A once-promising combination, the arm was halted after the data and safety monitoring board detected an increased risk of hospitalization and death, which led the National Institutes of Health to warn against using the combination for idiopathic pulmonary fibrosis (IPF).
Some clinicians, however, continued to use acetylcysteine, an over-the-counter antioxidant supplement, as monotherapy.
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 as well.
Baseline characteristics were well matched in the two study groups. The mean age was 67 years, 22% of the patients were women, and 96% were white. The mean baseline FVC was 73% of the predicted value, and the mean carbon monoxide diffusing capacity was 45% of the predicted value. The 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.
The work was funded by the National Heart, Lung, and Blood Institute, among others. Dr. Raghu reported grant support and personal fees from Gilead; personal fees from Biogen, Boehringer Ingelheim, and other companies; and other support from MedImmune outside the submitted work. The other authors disclosed payments for various services from those or other companies.