Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis
- PMID: 24836310
- DOI: 10.1056/NEJMoa1402584
Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis
Erratum in
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Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis.N Engl J Med. 2015 Aug 20;373(8):782. doi: 10.1056/NEJMx150012. N Engl J Med. 2015. PMID: 26287867 No abstract available.
Abstract
Background: Nintedanib (formerly known as BIBF 1120) is an intracellular inhibitor that targets multiple tyrosine kinases. A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis.
Methods: We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis. The primary end point was the annual rate of decline in forced vital capacity (FVC). Key secondary end points were the time to the first acute exacerbation and the change from baseline in the total score on the St. George's Respiratory Questionnaire, both assessed over a 52-week period.
Results: A total of 1066 patients were randomly assigned in a 3:2 ratio to receive nintedanib or placebo. The adjusted annual rate of change in FVC was -114.7 ml with nintedanib versus -239.9 ml with placebo (difference, 125.3 ml; 95% confidence interval [CI], 77.7 to 172.8; P<0.001) in INPULSIS-1 and -113.6 ml with nintedanib versus -207.3 ml with placebo (difference, 93.7 ml; 95% CI, 44.8 to 142.7; P<0.001) in INPULSIS-2. In INPULSIS-1, there was no significant difference between the nintedanib and placebo groups in the time to the first acute exacerbation (hazard ratio with nintedanib, 1.15; 95% CI, 0.54 to 2.42; P=0.67); in INPULSIS-2, there was a significant benefit with nintedanib versus placebo (hazard ratio, 0.38; 95% CI, 0.19 to 0.77; P=0.005). The most frequent adverse event in the nintedanib groups was diarrhea, with rates of 61.5% and 18.6% in the nintedanib and placebo groups, respectively, in INPULSIS-1 and 63.2% and 18.3% in the two groups, respectively, in INPULSIS-2.
Conclusions: In patients with idiopathic pulmonary fibrosis, nintedanib reduced the decline in FVC, which is consistent with a slowing of disease progression; nintedanib was frequently associated with diarrhea, which led to discontinuation of the study medication in less than 5% of patients. (Funded by Boehringer Ingelheim; INPULSIS-1 and INPULSIS-2 ClinicalTrials.gov numbers, NCT01335464 and NCT01335477.).
Comment in
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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.
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Treatments for idiopathic pulmonary fibrosis.N Engl J Med. 2014 Aug 21;371(8):783. doi: 10.1056/NEJMc1407776. N Engl J Med. 2014. PMID: 25140967 No abstract available.
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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.
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Treatments for idiopathic pulmonary fibrosis.N Engl J Med. 2014 Aug 21;371(8):781-2. doi: 10.1056/NEJMc1407776. N Engl J Med. 2014. PMID: 25140969 No abstract available.
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Nintedanib reduced decline in FVC in idiopathic pulmonary fibrosis.Ann Intern Med. 2014 Oct 21;161(8):JC5. doi: 10.7326/0003-4819-161-8-201410210-02005. Ann Intern Med. 2014. PMID: 25329222 No abstract available.
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[Idiopathic pulmonary fibrosis. An experimental medication].Perspect Infirm. 2015 Jan-Feb;12(1):62. Perspect Infirm. 2015. PMID: 25651687 French. No abstract available.
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Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis, Cytisine versus Nicotine for Smoking Cessation, and FACED Score for Non-Cystic Fibrosis Bronchiectasis.Am J Respir Crit Care Med. 2015 Jul 15;192(2):249-51. doi: 10.1164/rccm.201503-0554RR. Am J Respir Crit Care Med. 2015. PMID: 26177172 No abstract available.
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Weight-Loss Effect on FVC in Nintedanib Idiopathic Pulmonary Fibrosis Trials?Am J Respir Crit Care Med. 2015 Oct 15;192(8):1020. doi: 10.1164/rccm.201505-0937LE. Am J Respir Crit Care Med. 2015. PMID: 26469846 No abstract available.
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Reply: Weight-Loss Effect on FVC in Nintedanib Idiopathic Pulmonary Fibrosis Trials?Am J Respir Crit Care Med. 2015 Oct 15;192(8):1020-1. doi: 10.1164/rccm.201507-1354LE. Am J Respir Crit Care Med. 2015. PMID: 26469847 No abstract available.
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