Efficacy of Pirfenidone in the Context of Multiple Disease Progression Events in Patients With Idiopathic Pulmonary Fibrosis

Steven D. Nathan, Ulrich Costabel, Ian Glaspole, Marilyn K Glassberg Csete, Lisa H. Lancaster, David J. Lederer, Carlos A. Pereira, Benjamin Trzaskoma, Elizabeth A. Morgenthien, Susan L. Limb, Athol U. Wells

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Declines in percent predicted FVC (% predicted FVC), declines in 6-min walk distance (6MWD), and respiratory hospitalizations are events associated with disease progression and mortality in idiopathic pulmonary fibrosis. The incidence of multiple events in the same patient over 12 months of pirfenidone treatment is unknown. Methods: Patients who received pirfenidone 2,403 mg/d (n = 623) or placebo (n = 624) in the ASCEND (study 016; NCT01366209) and CAPACITY (studies 004 and 006; NCT00287716 and NCT00287729) phase III trials were included in this post hoc analysis. Disease progression events were defined as relative decline in % predicted FVC ≥ 10%, absolute decline in 6MWD ≥ 50 m, respiratory hospitalization, or death from any cause. The incidence of disease progression events over 12 months was assessed. Results: The most frequent disease progression events were declines in % predicted FVC (pirfenidone vs placebo; 202 vs 304 events) and declines in 6MWD (pirfenidone vs placebo; 265 vs 348 events). Fewer patients who received pirfenidone had more than one progression event compared with placebo (17.0% vs 30.1%; P <.0001). Death following one or more progression event occurred less frequently in the pirfenidone group than in the placebo group (2.1% vs 6.3%; P =.0002). Conclusions: Pirfenidone significantly reduced the incidence of multiple progression events and death after a progression event over 12 months of treatment compared with placebo. These findings suggest that continued treatment with pirfenidone confers a benefit despite the occurrence of any single disease progression event. Trial Registry: ClinicalTrials.gov; Nos. NCT01366209, NCT00287716, and NCT00287729; URL: www.clinicaltrials.gov.

Original languageEnglish (US)
JournalCHEST
DOIs
StatePublished - Jan 1 2019

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Idiopathic Pulmonary Fibrosis
Disease Progression
Placebos
Incidence
Hospitalization
pirfenidone
Registries
Cause of Death
Therapeutics
Mortality

Keywords

  • disease progression
  • idiopathic pulmonary fibrosis
  • interstitial lung diseases
  • pirfenidone

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Efficacy of Pirfenidone in the Context of Multiple Disease Progression Events in Patients With Idiopathic Pulmonary Fibrosis. / Nathan, Steven D.; Costabel, Ulrich; Glaspole, Ian; Glassberg Csete, Marilyn K; Lancaster, Lisa H.; Lederer, David J.; Pereira, Carlos A.; Trzaskoma, Benjamin; Morgenthien, Elizabeth A.; Limb, Susan L.; Wells, Athol U.

In: CHEST, 01.01.2019.

Research output: Contribution to journalArticle

Nathan, SD, Costabel, U, Glaspole, I, Glassberg Csete, MK, Lancaster, LH, Lederer, DJ, Pereira, CA, Trzaskoma, B, Morgenthien, EA, Limb, SL & Wells, AU 2019, 'Efficacy of Pirfenidone in the Context of Multiple Disease Progression Events in Patients With Idiopathic Pulmonary Fibrosis', CHEST. https://doi.org/10.1016/j.chest.2018.11.008
Nathan, Steven D. ; Costabel, Ulrich ; Glaspole, Ian ; Glassberg Csete, Marilyn K ; Lancaster, Lisa H. ; Lederer, David J. ; Pereira, Carlos A. ; Trzaskoma, Benjamin ; Morgenthien, Elizabeth A. ; Limb, Susan L. ; Wells, Athol U. / Efficacy of Pirfenidone in the Context of Multiple Disease Progression Events in Patients With Idiopathic Pulmonary Fibrosis. In: CHEST. 2019.
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abstract = "Background: Declines in percent predicted FVC ({\%} predicted FVC), declines in 6-min walk distance (6MWD), and respiratory hospitalizations are events associated with disease progression and mortality in idiopathic pulmonary fibrosis. The incidence of multiple events in the same patient over 12 months of pirfenidone treatment is unknown. Methods: Patients who received pirfenidone 2,403 mg/d (n = 623) or placebo (n = 624) in the ASCEND (study 016; NCT01366209) and CAPACITY (studies 004 and 006; NCT00287716 and NCT00287729) phase III trials were included in this post hoc analysis. Disease progression events were defined as relative decline in {\%} predicted FVC ≥ 10{\%}, absolute decline in 6MWD ≥ 50 m, respiratory hospitalization, or death from any cause. The incidence of disease progression events over 12 months was assessed. Results: The most frequent disease progression events were declines in {\%} predicted FVC (pirfenidone vs placebo; 202 vs 304 events) and declines in 6MWD (pirfenidone vs placebo; 265 vs 348 events). Fewer patients who received pirfenidone had more than one progression event compared with placebo (17.0{\%} vs 30.1{\%}; P <.0001). Death following one or more progression event occurred less frequently in the pirfenidone group than in the placebo group (2.1{\%} vs 6.3{\%}; P =.0002). Conclusions: Pirfenidone significantly reduced the incidence of multiple progression events and death after a progression event over 12 months of treatment compared with placebo. These findings suggest that continued treatment with pirfenidone confers a benefit despite the occurrence of any single disease progression event. Trial Registry: ClinicalTrials.gov; Nos. NCT01366209, NCT00287716, and NCT00287729; URL: www.clinicaltrials.gov.",
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AU - Lancaster, Lisa H.

AU - Lederer, David J.

AU - Pereira, Carlos A.

AU - Trzaskoma, Benjamin

AU - Morgenthien, Elizabeth A.

AU - Limb, Susan L.

AU - Wells, Athol U.

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N2 - Background: Declines in percent predicted FVC (% predicted FVC), declines in 6-min walk distance (6MWD), and respiratory hospitalizations are events associated with disease progression and mortality in idiopathic pulmonary fibrosis. The incidence of multiple events in the same patient over 12 months of pirfenidone treatment is unknown. Methods: Patients who received pirfenidone 2,403 mg/d (n = 623) or placebo (n = 624) in the ASCEND (study 016; NCT01366209) and CAPACITY (studies 004 and 006; NCT00287716 and NCT00287729) phase III trials were included in this post hoc analysis. Disease progression events were defined as relative decline in % predicted FVC ≥ 10%, absolute decline in 6MWD ≥ 50 m, respiratory hospitalization, or death from any cause. The incidence of disease progression events over 12 months was assessed. Results: The most frequent disease progression events were declines in % predicted FVC (pirfenidone vs placebo; 202 vs 304 events) and declines in 6MWD (pirfenidone vs placebo; 265 vs 348 events). Fewer patients who received pirfenidone had more than one progression event compared with placebo (17.0% vs 30.1%; P <.0001). Death following one or more progression event occurred less frequently in the pirfenidone group than in the placebo group (2.1% vs 6.3%; P =.0002). Conclusions: Pirfenidone significantly reduced the incidence of multiple progression events and death after a progression event over 12 months of treatment compared with placebo. These findings suggest that continued treatment with pirfenidone confers a benefit despite the occurrence of any single disease progression event. Trial Registry: ClinicalTrials.gov; Nos. NCT01366209, NCT00287716, and NCT00287729; URL: www.clinicaltrials.gov.

AB - Background: Declines in percent predicted FVC (% predicted FVC), declines in 6-min walk distance (6MWD), and respiratory hospitalizations are events associated with disease progression and mortality in idiopathic pulmonary fibrosis. The incidence of multiple events in the same patient over 12 months of pirfenidone treatment is unknown. Methods: Patients who received pirfenidone 2,403 mg/d (n = 623) or placebo (n = 624) in the ASCEND (study 016; NCT01366209) and CAPACITY (studies 004 and 006; NCT00287716 and NCT00287729) phase III trials were included in this post hoc analysis. Disease progression events were defined as relative decline in % predicted FVC ≥ 10%, absolute decline in 6MWD ≥ 50 m, respiratory hospitalization, or death from any cause. The incidence of disease progression events over 12 months was assessed. Results: The most frequent disease progression events were declines in % predicted FVC (pirfenidone vs placebo; 202 vs 304 events) and declines in 6MWD (pirfenidone vs placebo; 265 vs 348 events). Fewer patients who received pirfenidone had more than one progression event compared with placebo (17.0% vs 30.1%; P <.0001). Death following one or more progression event occurred less frequently in the pirfenidone group than in the placebo group (2.1% vs 6.3%; P =.0002). Conclusions: Pirfenidone significantly reduced the incidence of multiple progression events and death after a progression event over 12 months of treatment compared with placebo. These findings suggest that continued treatment with pirfenidone confers a benefit despite the occurrence of any single disease progression event. Trial Registry: ClinicalTrials.gov; Nos. NCT01366209, NCT00287716, and NCT00287729; URL: www.clinicaltrials.gov.

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