Pneumologie 2016; 70 - P209
DOI: 10.1055/s-0036-1572066

Effect of Pirfenidone on Treatment-emergent (TE) All-cause Mortality (ACM) in Patients with Idiopathic Pulmonary Fibrosis (IPF): Pooled Data Analysis from ASCEND and CAPACITY

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

Background: Pooled analysis of the ASCEND and CAPACITY studies showed a significant reduction in the risk of ACM over 52 weeks in patients with IPF treated with pirfenidone compared with placebo, and a nonsignificant trend favoring pirfenidone over the entire study period (up to week 120).

Objective: To evaluate TE ACM over the full duration of observation in the pooled population from ASCEND and CAPACITY.

Methods: TE ACM at last vital status assessment was evaluated in 1247 patients. TE deaths occurred after the first pirfenidone dose and within 28 days of the last dose. KaplanMeier estimates were used to summarize survival time.

Results: At week 120, TE ACM occurred in 27/623 (4.3%) patients on pirfenidone compared with 44/624 (7.1%) on placebo. The most common cause of death in both treatment groups was IPF (1.6% and 3.4% for pirfenidone and placebo, respectively). The TE ACM rate was lower on pirfenidone, compared to placebo, with a 38% reduction in the risk of TE ACM over 120 weeks (HR = 0.62; 95% CI, 0.39 – 1.01; P= 0.0515; (Figure). Estimates of TE ACM after week 96 are associated with higher uncertainty since few patients remained thereafter in the study.

Fig. 1: Kaplan-Meier Plot of TE ACM through End of Study of All Randomized Patients

Patients at Risk (% on studydrug)

Pirfenidone

623 (100.0%)

588 (94.4%)

539 (86.5%)

276 (44.3%)

60 (9.6%)

1 (0.2%)

Placebo

624 (100.0%)

594 (95.2%)

550 (88.1%)

281 (45.0%)

56 (9.0%)

3 (0.5%)

Conclusions: Pooled outcome analysis of the ASCEND and CAPACITY studies showed a clear trend towards reduced risk of TE ACM in patients with IPF treated with pirfenidone.