A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis

Talmadge E. King, Williamson Z. Bradford, Socorro Castro-Bernardini, Elizabeth A. Fagan, Ian Glaspole, Marilyn K. Glassberg, Eduard Gorina, Peter M. Hopkins, David Kardatzke, Lisa Lancaster, David J. Lederer, Steven D. Nathan, Carlos A. Pereira, Steven A. Sahn, Robert Sussman, Jeffrey J. Swigris, Paul W. Noble

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Abstract

BACKGROUND: In two of three phase 3 trials, pirfenidone, an oral antifibrotic therapy, reduced disease progression, as measured by the decline in forced vital capacity (FVC) or vital capacity, in patients with idiopathic pulmonary fibrosis; in the third trial, this end point was not achieved. We sought to confirm the beneficial effect of pirfenidone on disease progression in such patients. METHODS: In this phase 3 study, we randomly assigned 555 patients with idiopathic pulmonary fibrosis to receive either oral pirfenidone (2403 mg per day) or placebo for 52 weeks. The primary end point was the change in FVC or death at week 52. Secondary end points were the 6-minute walk distance, progression-free survival, dyspnea, and death from any cause or from idiopathic pulmonary fibrosis. RESULTS: In the pirfenidone group, as compared with the placebo group, there was a relative reduction of 47.9% in the proportion of patients who had an absolute decline of 10 percentage points or more in the percentage of the predicted FVC or who died; there was also a relative increase of 132.5% in the proportion of patients with no decline in FVC (P<0.001). Pirfenidone reduced the decline in the 6-minute walk distance (P = 0.04) and improved progression-free survival (P<0.001). There was no significant between-group difference in dyspnea scores (P = 0.16) or in rates of death from any cause (P = 0.10) or from idiopathic pulmonary fibrosis (P = 0.23). However, in a prespecified pooled analysis incorporating results from two previous phase 3 trials, the between-group difference favoring pirfenidone was significant for death from any cause (P = 0.01) and from idiopathic pulmonary fibrosis (P = 0.006). Gastrointestinal and skin-related adverse events were more common in the pirfenidone group than in the placebo group but rarely led to treatment discontinuation. CONCLUSIONS: Pirfenidone, as compared with placebo, reduced disease progression, as reflected by lung function, exercise tolerance, and progression-free survival, in patients with idiopathic pulmonary fibrosis. Treatment was associated with an acceptable side-effect profile and fewer deaths.

Original languageEnglish (US)
Pages (from-to)2083-2092
Number of pages10
JournalNew England Journal of Medicine
Volume370
Issue number22
DOIs
StatePublished - Jan 1 2014

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Idiopathic Pulmonary Fibrosis
Vital Capacity
Placebos
Disease-Free Survival
Disease Progression
Cause of Death
Dyspnea
Exercise Tolerance
pirfenidone
Therapeutics
Lung
Skin
Mortality

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

King, T. E., Bradford, W. Z., Castro-Bernardini, S., Fagan, E. A., Glaspole, I., Glassberg, M. K., ... Noble, P. W. (2014). A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. New England Journal of Medicine, 370(22), 2083-2092. https://doi.org/10.1056/NEJMoa1402582
King, Talmadge E. ; Bradford, Williamson Z. ; Castro-Bernardini, Socorro ; Fagan, Elizabeth A. ; Glaspole, Ian ; Glassberg, Marilyn K. ; Gorina, Eduard ; Hopkins, Peter M. ; Kardatzke, David ; Lancaster, Lisa ; Lederer, David J. ; Nathan, Steven D. ; Pereira, Carlos A. ; Sahn, Steven A. ; Sussman, Robert ; Swigris, Jeffrey J. ; Noble, Paul W. / A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. In: New England Journal of Medicine. 2014 ; Vol. 370, No. 22. pp. 2083-2092.
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abstract = "BACKGROUND: In two of three phase 3 trials, pirfenidone, an oral antifibrotic therapy, reduced disease progression, as measured by the decline in forced vital capacity (FVC) or vital capacity, in patients with idiopathic pulmonary fibrosis; in the third trial, this end point was not achieved. We sought to confirm the beneficial effect of pirfenidone on disease progression in such patients. METHODS: In this phase 3 study, we randomly assigned 555 patients with idiopathic pulmonary fibrosis to receive either oral pirfenidone (2403 mg per day) or placebo for 52 weeks. The primary end point was the change in FVC or death at week 52. Secondary end points were the 6-minute walk distance, progression-free survival, dyspnea, and death from any cause or from idiopathic pulmonary fibrosis. RESULTS: In the pirfenidone group, as compared with the placebo group, there was a relative reduction of 47.9{\%} in the proportion of patients who had an absolute decline of 10 percentage points or more in the percentage of the predicted FVC or who died; there was also a relative increase of 132.5{\%} in the proportion of patients with no decline in FVC (P<0.001). Pirfenidone reduced the decline in the 6-minute walk distance (P = 0.04) and improved progression-free survival (P<0.001). There was no significant between-group difference in dyspnea scores (P = 0.16) or in rates of death from any cause (P = 0.10) or from idiopathic pulmonary fibrosis (P = 0.23). However, in a prespecified pooled analysis incorporating results from two previous phase 3 trials, the between-group difference favoring pirfenidone was significant for death from any cause (P = 0.01) and from idiopathic pulmonary fibrosis (P = 0.006). Gastrointestinal and skin-related adverse events were more common in the pirfenidone group than in the placebo group but rarely led to treatment discontinuation. CONCLUSIONS: Pirfenidone, as compared with placebo, reduced disease progression, as reflected by lung function, exercise tolerance, and progression-free survival, in patients with idiopathic pulmonary fibrosis. Treatment was associated with an acceptable side-effect profile and fewer deaths.",
author = "King, {Talmadge E.} and Bradford, {Williamson Z.} and Socorro Castro-Bernardini and Fagan, {Elizabeth A.} and Ian Glaspole and Glassberg, {Marilyn K.} and Eduard Gorina and Hopkins, {Peter M.} and David Kardatzke and Lisa Lancaster and Lederer, {David J.} and Nathan, {Steven D.} and Pereira, {Carlos A.} and Sahn, {Steven A.} and Robert Sussman and Swigris, {Jeffrey J.} and Noble, {Paul W.}",
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King, TE, Bradford, WZ, Castro-Bernardini, S, Fagan, EA, Glaspole, I, Glassberg, MK, Gorina, E, Hopkins, PM, Kardatzke, D, Lancaster, L, Lederer, DJ, Nathan, SD, Pereira, CA, Sahn, SA, Sussman, R, Swigris, JJ & Noble, PW 2014, 'A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis', New England Journal of Medicine, vol. 370, no. 22, pp. 2083-2092. https://doi.org/10.1056/NEJMoa1402582

A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. / King, Talmadge E.; Bradford, Williamson Z.; Castro-Bernardini, Socorro; Fagan, Elizabeth A.; Glaspole, Ian; Glassberg, Marilyn K.; Gorina, Eduard; Hopkins, Peter M.; Kardatzke, David; Lancaster, Lisa; Lederer, David J.; Nathan, Steven D.; Pereira, Carlos A.; Sahn, Steven A.; Sussman, Robert; Swigris, Jeffrey J.; Noble, Paul W.

In: New England Journal of Medicine, Vol. 370, No. 22, 01.01.2014, p. 2083-2092.

Research output: Contribution to journalArticle

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T1 - A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis

AU - King, Talmadge E.

AU - Bradford, Williamson Z.

AU - Castro-Bernardini, Socorro

AU - Fagan, Elizabeth A.

AU - Glaspole, Ian

AU - Glassberg, Marilyn K.

AU - Gorina, Eduard

AU - Hopkins, Peter M.

AU - Kardatzke, David

AU - Lancaster, Lisa

AU - Lederer, David J.

AU - Nathan, Steven D.

AU - Pereira, Carlos A.

AU - Sahn, Steven A.

AU - Sussman, Robert

AU - Swigris, Jeffrey J.

AU - Noble, Paul W.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - BACKGROUND: In two of three phase 3 trials, pirfenidone, an oral antifibrotic therapy, reduced disease progression, as measured by the decline in forced vital capacity (FVC) or vital capacity, in patients with idiopathic pulmonary fibrosis; in the third trial, this end point was not achieved. We sought to confirm the beneficial effect of pirfenidone on disease progression in such patients. METHODS: In this phase 3 study, we randomly assigned 555 patients with idiopathic pulmonary fibrosis to receive either oral pirfenidone (2403 mg per day) or placebo for 52 weeks. The primary end point was the change in FVC or death at week 52. Secondary end points were the 6-minute walk distance, progression-free survival, dyspnea, and death from any cause or from idiopathic pulmonary fibrosis. RESULTS: In the pirfenidone group, as compared with the placebo group, there was a relative reduction of 47.9% in the proportion of patients who had an absolute decline of 10 percentage points or more in the percentage of the predicted FVC or who died; there was also a relative increase of 132.5% in the proportion of patients with no decline in FVC (P<0.001). Pirfenidone reduced the decline in the 6-minute walk distance (P = 0.04) and improved progression-free survival (P<0.001). There was no significant between-group difference in dyspnea scores (P = 0.16) or in rates of death from any cause (P = 0.10) or from idiopathic pulmonary fibrosis (P = 0.23). However, in a prespecified pooled analysis incorporating results from two previous phase 3 trials, the between-group difference favoring pirfenidone was significant for death from any cause (P = 0.01) and from idiopathic pulmonary fibrosis (P = 0.006). Gastrointestinal and skin-related adverse events were more common in the pirfenidone group than in the placebo group but rarely led to treatment discontinuation. CONCLUSIONS: Pirfenidone, as compared with placebo, reduced disease progression, as reflected by lung function, exercise tolerance, and progression-free survival, in patients with idiopathic pulmonary fibrosis. Treatment was associated with an acceptable side-effect profile and fewer deaths.

AB - BACKGROUND: In two of three phase 3 trials, pirfenidone, an oral antifibrotic therapy, reduced disease progression, as measured by the decline in forced vital capacity (FVC) or vital capacity, in patients with idiopathic pulmonary fibrosis; in the third trial, this end point was not achieved. We sought to confirm the beneficial effect of pirfenidone on disease progression in such patients. METHODS: In this phase 3 study, we randomly assigned 555 patients with idiopathic pulmonary fibrosis to receive either oral pirfenidone (2403 mg per day) or placebo for 52 weeks. The primary end point was the change in FVC or death at week 52. Secondary end points were the 6-minute walk distance, progression-free survival, dyspnea, and death from any cause or from idiopathic pulmonary fibrosis. RESULTS: In the pirfenidone group, as compared with the placebo group, there was a relative reduction of 47.9% in the proportion of patients who had an absolute decline of 10 percentage points or more in the percentage of the predicted FVC or who died; there was also a relative increase of 132.5% in the proportion of patients with no decline in FVC (P<0.001). Pirfenidone reduced the decline in the 6-minute walk distance (P = 0.04) and improved progression-free survival (P<0.001). There was no significant between-group difference in dyspnea scores (P = 0.16) or in rates of death from any cause (P = 0.10) or from idiopathic pulmonary fibrosis (P = 0.23). However, in a prespecified pooled analysis incorporating results from two previous phase 3 trials, the between-group difference favoring pirfenidone was significant for death from any cause (P = 0.01) and from idiopathic pulmonary fibrosis (P = 0.006). Gastrointestinal and skin-related adverse events were more common in the pirfenidone group than in the placebo group but rarely led to treatment discontinuation. CONCLUSIONS: Pirfenidone, as compared with placebo, reduced disease progression, as reflected by lung function, exercise tolerance, and progression-free survival, in patients with idiopathic pulmonary fibrosis. Treatment was associated with an acceptable side-effect profile and fewer deaths.

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King TE, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. New England Journal of Medicine. 2014 Jan 1;370(22):2083-2092. https://doi.org/10.1056/NEJMoa1402582