Efficacy of Pirfenidone in Patients with Advanced-stage Idiopathic Pulmonary Fibrosis

Abstract

Objective To assess the efficacy of pirfenidone in patients with advanced-stage idiopathic pulmonary fibrosis (IPF), we conducted a retrospective study of patients who received pirfenidone therapy. In addition, the combined effects of inhaled N-acetylcysteine (NAC) and pirfenidone were evaluated. Methods Eligible patients had a clinical and radiologic diagnosis of advanced-stage IPF (stages of severity III&IV). Patients who exhibited a relative decline in forced vital capacity (FVC) of 10% or more within the preceding six (±2) months were enrolled. The outcome was evaluated from the date of the 6-month follow-up PFT. Relative declines in FVC of more than 10% were defined as progressive disease (ineffective group), while those less than 10% were defined as stable disease (effective group). The clinical features were compared between the two groups. We also compared the efficacy of the combined therapy with inhaled NAC and pirfenidone (n=11) with that of pirfenidone alone (n=7). Results Eighteen patients 59-82 years of age with IPF who received pirfenidone therapy were reviewed. Pirfenidone stabilized declines in FVC by 10% at six months in eight of the 18 cases (44%). The median changes in FVC at six months were +120 mL in the effective group and -590 mL in the ineffective group. The number of NAC users was significantly higher in the effective group (7/8=87.5%) than in the ineffective group (3/10=30%) (p=0.02). Furthermore, the use of combined NAC therapy was correlated with a favorable outcome. The median change in FVC at six months was 0 mL in the NAC group and -290 mL in the non-NAC group. The median survival period was 557±66 days in the NAC group and 196±57 days in the non-NAC group (p=0.03). Conclusion Among the advanced-stage IPF patients with a more progressive status, pirfenidone decreased the rate of decline in FVC. In addition, patients treated with pirfenidone combined with NAC therapy exhibited favorable outcomes. Additional studies are needed to confirm the efficacy of this combined therapy for IPF.

Efficacy and Safety of Pirfenidone in Advanced Idiopathic Pulmonary Fibrosis

“…In an open-label phase 2 study ( n = 54), Raghu et al[10] demonstrated that pirfenidone could stabilize or improve lung function (in 70.7% of patients at 6 months) in IPF patients, some of whom were at an advanced stage (FVC range, 26–108% predicted; DLco range, 8–104% predicted). A retrospective study of advanced IPF ( n = 18, stage III and IV according to JRS criteria) also showed that pirfenidone stabilized FVC decline in 44% of patients over 6 months and that the median change in their FVC was +120 mL [12]. Postmarketing surveillance of 1,371 IPF patients, some of whom were at an advanced stage (stage III and IV in 67.4% of patients), showed that pirfenidone stabilized both the vital capacity and subjective symptoms in most patients (70–80%) treated for ≥6 months [13].…”

Interstitial lung disease

“…Based on some of these studies the first IPF-specific drug, pirfenidone, has recently been licenced for use in Europe [95]. In the past year, safety reports of pirfenidone in real-life practice have been published both from Japan and Europe, confirming that pirfenidone is well tolerated and can improve progression-free survival in IPF [96][97][98]. However, this is just the first step on a long road towards successful treatment of IPF, and we should keep walking with it clear in our mind that combinations of various agents may be more effective [99].…”

Efficacy of antioxidant in idiopathic pulmonary fibrosis: a systematic review and meta-analysis

“…1). Eight studies were conducted in Japan (Bando et al, 2010[3]; Homma et al, 2012[14]; Huang et al, 2015[15]; Kamio et al, 2014[17]; Okuda et al, 2016[22]; Sakamoto et al, 2013[30], 2015[31]; Tomioka et al, 2005[36]), three in multi-countries (Behr et al, 2009[6], 2016[5]; Raghu et al, 2012[24]) and one in United States (Martinez et al, 2014[20]). Only two types of antioxidants (N-Acetylcysteine (NAC) (Bando et al, 2010[3]; Behr et al, 2009[6], 2016[5]; Homma et al, 2012[14]; Huang et al, 2015[15]; Martinez et al, 2014[20]; Okuda et al, 2016[22]; Raghu et al, 2012[24]; Sakamoto et al, 2013[30], 2015[31]; Tomioka et al, 2005[36]) and lecithinized superoxide dismutase (PC-SOD) (Kamio et al, 2014[17]) were reported in these studies.…”

“…Various clinical studies have reported the efficacy of antioxidant treatment (such as N-acetylcysteine (NAC) and lecithinized superoxide dismutase (PC-SOD)) for IPF (Bando et al, 2010[3]; Behr et al, 2009[6], 2016[5]; Homma et al, 2012[14]; Huang et al, 2015[15]; Kamio et al, 2014[17]; Martinez et al, 2014[20]; Okuda et al, 2016[22]; Raghu et al, 2012[24]; Sakamoto et al, 2013[30], 2015[31]; Tomioka et al, 2005[36]). Several studies found that NAC treatment had a beneficial effect on lung function in IPF patients and significantly delayed disease progression (Behr et al, 2009[6]; Homma et al, 2012[14]; Huang et al, 2015[15]; Okuda et al, 2016[22]; Sakamoto et al, 2013[30], 2015[31]) whereas few studies reported that NAC treatment had no benefit and did not significantly improve the lung function of patients with IPF (Bando et al, 2010[3]; Behr et al, 2016[5]; Martinez et al, 2014[20]; Raghu et al, 2012[24]). A study by Tomioka et al (Tomioka et al, 2005[36]) showed that N-acetylcysteine aerosol treatment might delay disease progression, but did not improve pulmonary function or quality of life (QoL).…”

“…However, PC-SOD treatment had a beneficial effect on serum markers in IPF patients with severe respiratory dysfunction (Kamio et al, 2014[17]). As low statistical power may limit the interpretability of the findings, the results of all of these trials (Bando et al, 2010[3]; Behr et al, 2009[6], 2016[5]; Homma et al, 2012[14]; Huang et al, 2015[15]; Kamio et al, 2014[17]; Martinez et al, 2014[20]; Okuda et al, 2016[22]; Raghu et al, 2012[24]; Sakamoto et al, 2013[30], 2015[31]; Tomioka et al, 2005[36]) should be interpreted with caution. In view of this conflicting evidence landscape, it is important to create an empirical evidence framework to underline the degree of therapeutic benefit of antioxidant therapy in IPF patients.…”