Predicting Life Expectancy for Pirfenidone in Idiopathic Pulmonary Fibrosis

Abstract

This study was funded by InterMune International AG, a wholly owned Roche subsidiary since 2014. Fisher was previously employed by InterMune UK, a wholly owned Roche subsidiary, until July 2015. He is currently employed by FIECON, which has received funding from F. Hoffmann-La Roche for consulting services. Nathan has received consulting fees from Roche-Genentech and Boehringer Ingelheim. He is also on the speakers' bureau for Roche-Genentech and Boehringer Ingelheim and has received research funding from both companies. Hill was previously employed by InterMune UK until October 2014. Hill and Marshall are employees of MAP BioPharma, which has received funding from F. Hoffmann-La Roche for consulting services. Dejonckheere and Thuresson are employees of F. Hoffmann-La Roche. Maher has received grants, consulting fees, and speaker fees from GlaxoSmithKline and UCB, and grants from Novartis. He has also received consulting fees and speaker fees from AstraZeneca, Bayer, Biogen Idec, Boehringer Ingelheim, Cipla, Lanthio, InterMune International AG, F. Hoffmann-La Roche, Sanofi-Aventis, and Takeda. Maher is supported by a National Institute for Health Research Clinician Scientist Fellowship (NIHR Ref: CS: -2013-13-017). Study concept and design were contributed by Fisher, Hill, Marshall, and Dejonckheere. Fisher, Nathan, and Thuresson collected the data, along with Hill and Marshall. Data interpretation was performed by Fisher, Maher, Nathan, and Dejonckheere. The manuscript was written primarily by Fisher, along with Maher and Dejonckheere, and revised by Fisher and Maher, along with the other authors.

Physiology of the lung in idiopathic pulmonary fibrosis

“…Although the novel antifibrotic agents pirfenidone and nintedanib attenuate the progressive decline in lung function characteristic of IPF [1], reduce the risk of hospitalisation or exacerbation [2,3], and reduce the risk of death [3][4][5], IPF is a very severe disease where clinical decline is common. IPF is of particular interest to the lung physiologist because its clinical expression, which ranges from exertional dyspnoea occurring early in the disease to end-stage respiratory failure, is directly related to alterations in lung physiology.…”

When to start and when to stop antifibrotic therapies

“…Patients were stratified according to FVC values (FVC >90% and ⩽90%; FVC >70% and ⩽70%). As for pirfenidone, there were no statistically significant differences between these subgroups in the annual rate of decline in FVC, change from baseline in St George's Respiratory Questionnaire total score, or time to first acute exacerbation [28,30]. These results showed consistent and meaningful evidence of a similar functional decline in both categories, more preserved and less preserved lung function and, most importantly, that antifibrotic drugs are equally effective in both scenarios.…”

“…Both for pirfenidone and nintedanib, the analyses provided further evidence to support the clinically meaningful treatment benefit and acceptable safety profile of antifibrotic treatments in patients with IPF [25,27,28].…”

Rationale, Design and Objectives of Two Phase III, Randomised, Placebo-Controlled Studies of GLPG1690, a Novel Autotaxin Inhibitor, in Idiopathic Pulmonary Fibrosis (ISABELA 1 and 2)

“…14 15 In addition, real-world registry data suggest improved survival in those treated with, versus without, antifibrotic treatments, regardless of baseline disease severity, 16 and pooled registry and clinical trial data suggest that pirfenidone increases life expectancy compared with best supportive care. 17 However, individuals may not tolerate adverse events (AEs) associated with pirfenidone (gastrointestinal and skin-related events) 12 14 or nintedanib (diarrhoea) 13 ; real-world data showed that AEs led to drug discontinuation in 20.9% and 26.3% of pirfenidone-treated and nintedanib-treated patients with IPF, respectively. 18 QoL is often significantly impaired in IPF, 1 9 19 and neither pirfenidone nor nintedanib has demonstrated benefits to QoL in clinical trials.…”