COMMENTARY

Idiopathic Pulmonary Fibrosis: A Novel Combination Therapy Shows Promise

Nicholas Gross, MD, PhD

Disclosures

April 20, 2015

Viewpoint

This study was small and case-controlled rather than randomized and double-blind. It must therefore be considered exploratory. Other issues are that the dose of pirfenidone was considerably smaller than the approved dose in the United States (up to 2400 mg/day) and therefore possibly suboptimal in the present trial. A 12-month trial is generally considered to be of insufficient duration for studies of IPF treatments, and a mortality endpoint would be more compelling. However, the outcome is interesting and perhaps deserves to be followed up because pirfenidone is becoming widely used in IPF, and NAC is an inexpensive generic drug that is fairly well-tolerated. Pirfenidone and nintedanib act on different inflammatory pathways,[4] so it is possible that a combination of the two agents would provide additive benefit.

Pirfenidone is believed to act by inhibiting transforming growth factor-beta, thus reducing the fibrotic process in the lungs. NAC has been experimentally used in several conditions. As a hydrogen donor, its use as a mucolytic has been widely explored in airway disorders to address hypersecretion. A trial of NAC monotherapy in IPF failed. In the United States, NAC is FDA-approved and available for nebulizer use in cystic fibrosis. Its administration through nebulization makes it possible to achieve higher local concentrations in the airways than is possible with oral administration.

As stated elsewhere, "the fight to combat this disease with new ammunition has begun."[4]

Abstract

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