A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis
- PMID: 24836312
- DOI: 10.1056/NEJMoa1402582
A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis
Erratum in
- N Engl J Med. 2014 Sep 18;371(12):1172
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. (Funded by InterMune; ASCEND ClinicalTrials.gov number, NCT01366209.).
Comment in
-
A new hope for idiopathic pulmonary fibrosis.N Engl J Med. 2014 May 29;370(22):2142-3. doi: 10.1056/NEJMe1403448. Epub 2014 May 18. N Engl J Med. 2014. PMID: 24836311 No abstract available.
-
Treatments for idiopathic pulmonary fibrosis.N Engl J Med. 2014 Aug 21;371(8):781. doi: 10.1056/NEJMc1407776. N Engl J Med. 2014. PMID: 25140968 No abstract available.
-
Treatments for idiopathic pulmonary fibrosis.N Engl J Med. 2014 Aug 21;371(8):782. doi: 10.1056/NEJMc1407776. N Engl J Med. 2014. PMID: 25140970 No abstract available.
-
Treatments for idiopathic pulmonary fibrosis.N Engl J Med. 2014 Aug 21;371(8):782. doi: 10.1056/NEJMc1407776. N Engl J Med. 2014. PMID: 25140971 No abstract available.
-
Treatments for idiopathic pulmonary fibrosis.N Engl J Med. 2014 Aug 21;371(8):783-4. doi: 10.1056/NEJMc1407776. N Engl J Med. 2014. PMID: 25147884 No abstract available.
-
Pirfenidone for idiopathic pulmonary fibrosis, thrombocytosis in chronic obstructive pulmonary disease exacerbations, and a longitudinal study on e-cigarettes.Am J Respir Crit Care Med. 2014 Sep 15;190(6):699-700. doi: 10.1164/rccm.201406-1188RR. Am J Respir Crit Care Med. 2014. PMID: 25221880 No abstract available.
-
Pirfenidone reduced disease progression in idiopathic pulmonary fibrosis.Ann Intern Med. 2014 Oct 21;161(8):JC4-5. doi: 10.7326/0003-4819-161-8-201410210-02004. Ann Intern Med. 2014. PMID: 25329221 No abstract available.
Similar articles
-
Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials.Lancet. 2011 May 21;377(9779):1760-9. doi: 10.1016/S0140-6736(11)60405-4. Epub 2011 May 13. Lancet. 2011. PMID: 21571362 Clinical Trial.
-
Pirfenidone in patients with idiopathic pulmonary fibrosis and more advanced lung function impairment.Respir Med. 2019 Jul;153:44-51. doi: 10.1016/j.rmed.2019.04.016. Epub 2019 Apr 24. Respir Med. 2019. PMID: 31153107 Clinical Trial.
-
Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: a double-blind, randomised, placebo-controlled, phase 2 trial.Lancet Respir Med. 2020 Feb;8(2):147-157. doi: 10.1016/S2213-2600(19)30341-8. Epub 2019 Sep 29. Lancet Respir Med. 2020. PMID: 31578169 Clinical Trial.
-
Pirfenidone: a review of its use in idiopathic pulmonary fibrosis.Drugs. 2015 Feb;75(2):219-30. doi: 10.1007/s40265-015-0350-9. Drugs. 2015. PMID: 25604027 Review.
-
Changing the idiopathic pulmonary fibrosis treatment approach and improving patient outcomes.Eur Respir Rev. 2012 Jun 1;21(124):161-7. doi: 10.1183/09059180.00001112. Eur Respir Rev. 2012. PMID: 22654089 Free PMC article. Review.
Cited by
-
Lysophosphatidic acid receptor 1 inhibition: a potential treatment target for pulmonary fibrosis.Eur Respir Rev. 2024 Jun 12;33(172):240015. doi: 10.1183/16000617.0015-2024. Print 2024 Apr. Eur Respir Rev. 2024. PMID: 39009409 Free PMC article. Review.
-
Structural Modification and Optimisation of Hyperoside Oriented to Inhibit TGF-β-Induced EMT Activity in Alveolar Epithelial Cells.Pharmaceuticals (Basel). 2024 May 2;17(5):584. doi: 10.3390/ph17050584. Pharmaceuticals (Basel). 2024. PMID: 38794154 Free PMC article.
-
Available Therapeutic Options for Corneal Neovascularization: A Review.Int J Mol Sci. 2024 May 17;25(10):5479. doi: 10.3390/ijms25105479. Int J Mol Sci. 2024. PMID: 38791518 Free PMC article. Review.
-
Identification of CFH and FHL2 as biomarkers for idiopathic pulmonary fibrosis.Front Med (Lausanne). 2024 May 9;11:1363643. doi: 10.3389/fmed.2024.1363643. eCollection 2024. Front Med (Lausanne). 2024. PMID: 38784225 Free PMC article.
-
Machine learning classifier is associated with mortality in interstitial lung disease: a retrospective validation study leveraging registry data.BMC Pulm Med. 2024 May 23;24(1):254. doi: 10.1186/s12890-024-03021-w. BMC Pulm Med. 2024. PMID: 38783245 Free PMC article.
Publication types
MeSH terms
Substances
Associated data
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical