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  • Effect of continued treatment with pirfenidone following clinically meaningful declines in forced vital capacity: analysis of data from three phase 3 trials in patients with idiopathic pulmonary fibrosis

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Interstitial lung disease
Original article
Effect of continued treatment with pirfenidone following clinically meaningful declines in forced vital capacity: analysis of data from three phase 3 trials in patients with idiopathic pulmonary fibrosis
  1. Steven D Nathan1,
  2. Carlo Albera2,
  3. Williamson Z Bradford3,
  4. Ulrich Costabel4,
  5. Roland M du Bois5,
  6. Elizabeth A Fagan3,
  7. Robert S Fishman3,
  8. Ian Glaspole6,
  9. Marilyn K Glassberg7,
  10. Kenneth F Glasscock3,
  11. Talmadge E King Jr8,
  12. Lisa Lancaster9,
  13. David J Lederer10,
  14. Zhengning Lin3,
  15. Carlos A Pereira11,
  16. Jeffrey J Swigris12,
  17. Dominique Valeyre13,
  18. Paul W Noble14,
  19. Athol U Wells15
  1. 1Inova Fairfax Hospital, Heart and Lung Transplant Center, Falls Church, Virginia, USA
  2. 2Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
  3. 3InterMune Inc., Brisbane, California, USA
  4. 4Department of Pneumology/Allergy, Ruhrlandklinik, Essen, Germany
  5. 5Imperial College, London, UK
  6. 6Alfred Hospital and Monash University, Melbourne, Australia
  7. 7University of Miami Miller School of Medicine, Miami, Florida, USA
  8. 8University of California, San Francisco, California, USA
  9. 9Vanderbilt University Medical Center, Nashville, Tennessee, USA
  10. 10Columbia University Medical Center, New York, New York, USA
  11. 11Paulista School of Medicine, Federal University of São Paulo, São Paulo, Brazil
  12. 12Interstitial Lung Disease Program, National Jewish Health, Denver, Colorado, USA
  13. 13Assistance Publique-Hôpitaux de Paris, Avicenne University Hospital, Bobigny, France
  14. 14Cedars Sinai Medical Center, Los Angeles, California, USA
  15. 15Royal Brompton Hospital, London, UK
  1. Correspondence to Dr Steven D Nathan, Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042. USA; Steven.Nathan{at}inova.org

Abstract

Background The assessment of treatment response in idiopathic pulmonary fibrosis (IPF) is complicated by the variable clinical course. We examined the variability in the rate of disease progression and evaluated the effect of continued treatment with pirfenidone in patients who experienced meaningful progression during treatment.

Methods The source population included patients enrolled in the ASCEND and CAPACITY trials (N=1247). Pearson's correlation coefficients were used to characterise the relationship between changes in FVC during consecutive 6-month intervals in the placebo population. Outcomes following a ≥10% decline in FVC were evaluated by comparing the proportion of patients in the pirfenidone and placebo groups who experienced a ≥10% decline in FVC or death during the subsequent 6 months.

Results A weak negative correlation was observed between FVC changes during consecutive intervals in the placebo population (coefficient, −0.146, p<0.001), indicating substantial variability. Thirty-four (5.5%) and 68 (10.9%) patients in the pirfenidone and placebo groups, respectively, experienced a ≥10% decline in FVC by month 6. During the subsequent 6 months, fewer patients in the pirfenidone group compared with placebo experienced a ≥10% decline in FVC or death (5.9% vs 27.9%; relative difference, 78.9%). There was one (2.9%) death in the pirfenidone group and 14 (20.6%) deaths in the placebo group (relative difference, 85.7%).

Conclusions Longitudinal FVC data from patients with IPF showed substantial intrasubject variability, underscoring the inability to reliably assess therapeutic response using serial FVC trends. In patients who progressed during treatment, continued treatment with pirfenidone resulted in a lower risk of subsequent FVC decline or death.

Trial registration numbers NCT01366209, NCT00287729, NCT00287716.

  • Idiopathic pulmonary fibrosis

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/thoraxjnl-2015-207011

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