Pneumologie 2016; 70 - V181
DOI: 10.1055/s-0036-1572141

Effect of continued treatment with pirfenidone following a clinically meaningful decline in percent predicted forced vital capacity in patients with idiopathic pulmonary fibrosis (IPF)

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

Background: IPF shows substantial inter- and intra-subject variability in the rates of disease progression, confounding the assessment of therapeutic response in an individual patient. The present analysis used pooled data from three Phase 3 trials to assess the potential benefit of continued treatment with pirfenidone (PFD) in patients who experience a ≥10% decline in forced vital capacity (% FVC) in first 6 months of treatment.

Methods: Source data included all patients randomized to PFD 2403 mg/d or placebo (PBO) in the ASCEND or CAPACITY studies (N = 1247). From these, we selected all patients with a ≥10% absolute decline in % FVC by month 3 or 6 and compared the proportion of patients in the PFD and PBO groups who experienced any of the following in the subsequent 6 months: (1) ≥10% decline in % FVC or death; (2) no further decline in % FVC; or (3) death. Missing values due to death were assigned the worst possible value (FVC = 0), missing values due to other reasons were replaced with the average value from the 3 patients with the least sum of squared differences at each visit.

Results: 34 (5.5%) and 68 (10.9%) patients in the pooled PFD and PBO groups, respectively, experienced a ≥10% decline in % FVC in the first 6 months (rel. difference 49.5%). During the subsequent 6 months, fewer PFD vs. PBO patients experienced a ≥10% decline in % FVC or death (2/34 [5.9%] vs. 19/68 [27.9%]), and more PFD vs. PBO patients had no further decline in % FVC (20/34 [58.8%] vs. 26/68 [38.2%]; Table 1). Additionally, there were fewer deaths in the PFD vs. PBO group (1/34 [2.9%] vs.14/68 [20.6%]).

Tab. 1: Outcomes during the 6-month period following an initial decline in percent predicted FVC ≥10% during the first 6 months of treatment

Pirfenidone

(N = 34)

Placebo

(N = 68)

Relative

Difference

P-value*

≥10% decline in FVC or death

2 (5.9%)

19 (27.9%)

78.9%

0.009

No further decline in FVC†

20 (58.8%)

26 (38.2%)

53.8%

0.059

Death

1 (2.9%)

14 (20.6%)

85.7%

0.018

FVC = forced vital capacity

*Fisher's exact test

†Either no decline or increase in FVC

Conclusions: In a post hoc analysis of outcomes in patients who experienced a ≥10% decline in % FVC during the first 6 months in the ASCEND or CAPACITY studies, continued treatment with pirfenidone appeared to result in a lower risk of % FVC decline or death during the subsequent 6 months. This suggests a potential benefit of continued treatment with pirfenidone despite an initial decline in FVC.