Pirfenidone for the treatment of idiopathic pulmonary fibrosis

Abstract

Pirfenidone is an orally administered drug with anti-fibrotic, anti-inflammatory and anti-oxidant properties. The efficacy of pirfenidone is supported by a number of Phase III trials as well as a Cochrane meta-analysis and tolerability data are also provided by clinical trials and a long-term extension phase of these studies. These trials led to the approval of pirfenidone for the treatment of idiopathic pulmonary fibrosis (IPF) in Japan in 2008 and in Europe in 2011 and it is now indicated for treatment of patients with mild-to-moderate IPF. The primary endpoint of these studies has usually been the change in percentage predicted forced vital capacity from baseline; there has been no improvement in respiratory symptoms and/or quality of life measurements and/or decrease in mortality. Clinical and basic research studies are needed to expand our knowledge, understanding the final role of pirfenidone in the treatment of IPF and also identifing genetic factors that influence the effectiveness of this treatment.

Keywords::

• idiopathic pulmonary fibrosis
• IPF
• pirfenidone
• pulmonary fibrosis
• tolerability

Financial & competing interests disclosure

V Poletti has served as investigator in clinical trials, speaker, Scientific Advisory Board member for Intermune. Attended international and national congressess sponsored by Intermune. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Pirfenidone is an orally administered drug with antifibrotic, anti-inflammatory and anti-oxidant properties in vitro and in vivo.

• Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease, with a median survival of 2–5 years, considered an epithelial-driven and fibroblast-activated process, in which inflammation is a secondary event.

• Clinical studies have been conducted in patients with IPF, but some reveal conflicting results.

• Primary endpoint of these studies have been usually the change in percentage predicted forced vital capacity from baseline or progression-free survival, mean change in 6-min walk test distance, mean change in percentage predicted of carbon monoxide diffusing capacity, mean change in dyspnea score, mean percentage change in worst SpO₂ during 6-min walk test and time to worsening of IPF.

• Following evaluation in Phase II and Phase III clinical trials led to the approval of pirfenidone for the treatment of IPF in Japan in 2008 and in Europe in 2011 and pirfenidone is now indicated for the treatment of patients with mild-to-moderate IPF.

• There has been no improvement in respiratory symptoms and/or quality-of-life measurements reported with pirfenidone; there is also no reported decrease in mortality.

• The most common adverse events seem to be gastrointestinal, skin disorders and dizziness.

• Patients should be well informed regarding the side effects to avoid drug discontinuation.

• Clinical and basic research studies are needed to expand our knowledge and understanding the final role of pirfenidone in the treatment of IPF.

Notes