Steven D. Nathan, MD
Medical Director, Lung Transplant Program
Advanced Lung Disease Program
Inova Fairfax Hospital
Falls Church, Virginia

Sakamoto S, Muramatsu Y, Satoh K, Ishida F, Kikuchi N, Sano G, Sugino K, Isobe K, Takai Y, Homma S. Effectiveness of combined therapy with pirfenidone and inhaled N-acetylcysteine for advanced idiopathic pulmonary fibrosis: a case-control study. Respirology. 2015;20(3):445-452.

This study compares treatment with pirfenidone (control; n = 10) to pirfenidone (PFD) combined with inhaled N-acetylcysteine (NAC, n = 24) in patients with advanced IPF who previously received pirfenidone. Outcomes were evaluated through 12-month follow-up pulmonary function testing. Treatment was considered ineffective if the decline in FVC was ≥ 10% and effective if the decline was <10%.

At the 12-month follow-up examination, treatment was deemed effective in 8 of 17 (47%) patients receiving NAC plus pirfenidone and in 2 of 10 (20%) receiving pirfenidone alone. The annual rate of change in FVC was -610 mL in the NAC plus pirfenidone group and -1320 mL in the pirfenidone group (P < 0.01, left-side figure). Disease progression was defined as death, a 10% decline in FVC or a 15% decline in DLco from baseline. Progression-free survival (PFS) was longer (304 days) in the NAC plus pirfenidone group than in the pirfenidone group (168 days; P = 0.016, right-side figure).

The authors conclude that combination treatment with inhaled NAC and oral pirfenidone reduced the rate of annual FVC decline and improved PFS in patients with advanced IPF.

Expert Commentary
Although the PANTHER trial showed no therapeutic benefit of orally-dosed NAC, delivery of the drug by inhalation appears to be beneficial. If the results of this study are validated, then the positive benefit might be due to higher local concentrations of drug than can be achieved with oral administration. Indeed, the results of this study need to be interpreted in the context of the very small number of patients from a single center. This study lends support to further trials of inhaled NAC alone or preferably NAC in combination with an approved IPF therapy.