Effect of pirfenidone in patients with more advanced idiopathic pulmonary fibrosis

Abstract

Data from controlled clinical studies in patients with more advanced idiopathic pulmonary fibrosis (IPF) could inform clinical practice, but they are limited, since this sub-population is usually excluded from clinical trials. These exploratory post-hoc analyses of the open-label, long-term extension study RECAP (NCT00662038) aimed to assess the efficacy and safety of pirfenidone in patients with more advanced IPF. Patients were categorised according to the extent of lung function impairment at baseline: more advanced (percent predicted FVC <50% and/or DLco <35%) and less advanced (percent predicted FVC ≥50% and DLco ≥35%).Overall, 596 patients with baseline FVC and/or DLco values available were included in the analyses; 187 patients had more advanced disease, and 409 patients had less advanced disease. Mean percent predicted FVC declined throughout 180 weeks of treatment in both more and less advanced disease subgroups. Both subgroups exhibited a similar pattern of adverse events; however, adverse events related to IPF progression were experienced by a higher proportion of patients with more advanced versus less advanced disease. Discontinuation rates due to any reason, adverse events related to IPF progression, or deaths were each higher in the more advanced versus the less advanced disease subgroup.These analyses found that longer-term pirfenidone treatment resulted in a similar rate of lung function decline and safety profile in patients with more advanced versus less advanced IPF, and the data suggest that pirfenidone is efficacious, well tolerated, and a feasible treatment option in patients with more advanced IPF.

Keywords: Advanced disease; Antifibrotic; Idiopathic pulmonary fibrosis; Lung function; Pirfenidone.

Conflict of interest statement

Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki, written informed consent was required from all patients participating in the study, and the institutional review board or ethics committee at each centre approved the study protocol.

Consent for publication

Not applicable.

Competing interests

UC was a member of the CAPACITY trial steering committee and an advisor on IPF trials to Bayer, Biogen, Boehringer Ingelheim, F. Hoffmann-La Roche, Ltd., FibroGen, GlaxoSmithKline, Global Blood Therapeutics, InterMune/Roche and UCB Celltech, and has received lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim and InterMune/Roche. CA was an advisor on IPF trials to F. Hoffmann-La Roche, Ltd. and FibroGen, and has received personal fees from Bayer, Boehringer Ingelheim, FibroGen, GlaxoSmithKline, InterMune/Roche, MSD and Sanofi. MKG was a member of the ASCEND study steering committee and an advisor for Bellerophon, Boehringer Ingelheim, Genentech, InterMune/Roche and Patara, and has received research grants from Genentech and InterMune/Roche. LHL reports research grants, prior advisory board, and disease state education from Genentech, research grants and disease state education from Boehringer Ingelheim, research grants from Celgene and Novartis, and research grants and consulting fees from Galapagos and Bellerophon outside of the submitted work. WAW is on the speaker bureaus for F. Hoffmann-La Roche, Ltd. and Boehringer Ingelheim; his institution has received research funding from both companies. UP was an employee of Clinipace-Accovion GmbH – a company contracted by F. Hoffmann-La Roche, Ltd. to perform analyses of study data – at the time of this study. FG is an employee of F. Hoffmann-La Roche, Ltd. K-UK is an employee and shareholder of F. Hoffmann-La Roche, Ltd. PWN was a member of the ASCEND and CAPACITY study steering committees and a consultant for Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, InterMune/Roche, Moerae Matrix and Takeda.

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Figures

Fig. 1

Mean percent predicted FVC over time by IPF severity at baseline in RECAP. *Patients with missing percent predicted FVC and DLco values were excluded. FVC Forced vital capacity, DLco Carbon monoxide diffusing capacity, IPF Idiopathic pulmonary fibrosis, SD Standard deviation