Pneumologie 2016; 70 - P204
DOI: 10.1055/s-0036-1572064

Pirfenidone is Efficacious in Patients with Idiopathic Pulmonary Fibrosis (IPF) and Mild Restrictive Disease

U Costabel 1, C Albera 2, WZ Bradford 3, EA Fagan 3, I Glaspole 4, MK Glassberg 5, E Gorina 3, D Kardatzke 3, TE King 6, L Lancaster 7, DJ Lederer 8, SD Nathan 9, CA Pereira 10, D Spirig 11, JJ Swigris 12, D Valeyre 13, PW Noble 14
  • 1Interstitielle und Seltene Lungenkrankheiten, Ruhrlandklinik
  • 2Department of Clinical and Biological Sciences, University of Turin
  • 3Intermune, Inc.
  • 4Alfred Hospital
  • 5Miller School of Medicine, University of Miami
  • 6University of California, San Francisco
  • 7Vanderbilt University Medical Center
  • 8Columbia University Medical Center
  • 9Inova Fairfax Hospital
  • 10Paulista School of Medicine, Federal University of São Paulo
  • 11Intermune Interational AG
  • 12National Jewish Health
  • 13Assistance Publique-Hôpitaux de Paris, Avicenne University Hospital
  • 14Cedars Sinai Medical Center

Introduction: IPF is a progressive, irreversible and fatal disease. Early treatment when lung function is relatively preserved may have beneficial outcomes. Here we investigated the efficacy of pirfenidone (PFD) in patients stratified by mild vs more pronounced restrictive disease as well as by GAP stage.

Methods: Efficacy outcomes (FVC, 6MWD, UCSD SOBQ) were analysed at 12 months in patients randomised to PFD 2403 mg/d or placebo (PBO) in the pooled CAPACITY/ASCEND population (N = 1247), stratified into two different sets of subgroups defined by dichotomisation of baseline FVC (≥80%, < 80%) and GAP stage (GAP1, GAP2 – 3).

Results: Demographic characteristics were similar across all four groups. In the PBO arm, disease progression as measured by FVC occurred with comparable frequency in mild vs. more pronounced restrictive disease, as well as in GAP1 vs. GAP2 – 3 stage. A higher proportion of PBO patients with more pronounced disease and GAP2 – 3 stage had a ≥50 m decline in 6MWD or death or a ≥20 point change in the UCSD SOBQ total score. PFD reduced the proportion of patients experiencing a ≥10% FVC decline or death and increased the proportion of patients with no FVC decline in all subgroups. PFD also reduced the proportion of patients with ≥50 m decline in the 6MWD or death and increased the proportion of patients with no decline in all subgroups. The magnitude of treatment effect in mild vs more pronounced restrictive disease was comparable, with no significant treatment-by subgroup interaction (Figure).

Conclusions:

In the placebo population, clinically significant disease progression occurs in both subgroups with mild and more pronounced restrictive disease, underlying the need for early intervention. The magnitude of pirfenidone effects on functional measures was comparable in both subgroups of patients (mild vs more pronounced restrictive disease or GAP 1 vs. GAP 2 – 3 stage), supporting early treatment soon after diagnosis, when pulmonary function is relatively preserved.

Fig. 1: 6MWD, 6-minute wak test distance; FVC, forced vital capacity; SOBQ, shortness of breath questionnaireFor FVC and 6MWD: treatment difference = pirfenidone – placebo; for SOBQ, treatment difference = placebo – pirfenidone