Idiopathic Pulmonary Fibrosis: A Novel Combination Therapy Shows Promise

Nicholas Gross, MD, PhD


April 20, 2015

Effectiveness of Combined Therapy With Pirfenidone and Inhaled N-acetylcysteine for Advanced Idiopathic Pulmonary Fibrosis: A Case-Control Study

Sakamoto S, Muramatsu Y, Satoh K, et al
Respirology. 2015;20:445-452


Idiopathic pulmonary fibrosis (IPF) is a devastating disorder that is typically rapidly progressive and fatal. For the most part, IPF has been resistant to various treatments, including corticosteroids, and its therapy has been limited to palliative care or, in suitable cases, lung transplantation.[1] Very recently, two new treatments were approved by the US Food and Drug Administration (FDA). They are pirfenidone (Esbreit®)[2] and nintedanib (Ofev®).[3] Both drugs have been shown to reduce the rate of decline in lung function when taken regularly over a period of about a year.

A clinical trial by a group of investigators in Japan has now investigated the possibility that further benefit might be obtained by combining pirfenidone with inhaled N-acetylcysteine (NAC). Patients with IPF who were already on treatment with pirfenidone and known to have a decline in lung function of 10% or more over the previous 6 months were enrolled. One group (n = 24) received pirfenidone (1200-1800 mg/day) plus inhalation of nebulized NAC at a dose of 352 mg twice daily; the other received pirfenidone at the same dose but received no NAC. The primary outcome was the percentage of patients whose lung function declined by 10% or less at 12 months.

In the pirfenidone-only group, only 2 of 10 patients experienced 10% or less decline in lung function. In the pirfenidone + NAC group, 8 of 17 patients experienced 10% or less decline in lung function. The mean declines were 1320-mL loss/year of forced vital capacity (FVC) vs 610-mL loss per year in the two groups, respectively (P < .01). The time to first exacerbation was also significantly longer in the pirfenidone + NAC group. Four patients left the pirfenidone + NAC group owing to "gastrointestinal discomfort," and one patient developed a photosensitivity rash; both of these are known adverse effects of pirfenidone. Two patients were noncompliant with NAC inhalation and were dropped from the study. There were no dropouts in the pirfenidone-only arm. The study authors concluded that "treatment with inhaled NAC and oral pirfenidone reduced the rate of annual FVC decline and improved time to first exacerbation in patients with advanced IPF."


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