Pirfenidone for the Treatment of Idiopathic Pulmonary Fibrosis
Katerina M Antoniou, MD, PhD1, and Demosthenes Bouros, MD, PhD, FCCP2
Int J Clin Rev 2012;02:05
doi: 10.5275/ijcr.2012.02.05
Idiopathic pulmonary fibrosis (IPF) is the most lethal form of diffuse lung fibrosis, with approximately half of those affected dying within 2–3 years of diagnosis. In February 2011, marketing authorization was granted by the European Commission for the use of pirfenidone to treat IPF. Pirfenidone is an orally bioavailable small molecule with antifibrotic and anti-inflammatory properties. In vitro and in vivo animal models of PF have shown that pirfenidone exerts its effect by reducing the levels of inflammatory cytokines such as tumor necrosis factor-α, by downregulating the transcription of key profibrotic growth factors such as transforming growth factor-β, and reducing lipid peroxidation and oxidative stress. Pirfenidone has been evaluated in four randomized, double-blind, placebo-controlled clinical trials. The data from these trials showed that pirfenidone can reduce the rate of decline in lung function measured as change in percentage of predicted forced vital capacity (FVC) or vital capacity. Secondary endpoints of progression-free survival (PFS), categorical change in percentage of predicted FVC, and 6-min walk distance were also improved. A meta-analysis of the three Phase III studies in patients with IPF demonstrated that pirfenidone significantly reduced disease progression. The efficacy of pirfenidone is associated with a good safety profile.