Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis.
By L. Richeldi, R. D. du Bois, G. Raghu, A. Azuma, K. Brown, U. Costabel, V. Cottin, K. Flaherty, D. Hansell, Y. Inoue and 13 more. New England Journal of Medicine, 2014
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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.).
Subfields: Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/39f3ef1c337fde6cc7c2deddf220650cda8e9942
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In Pulmonary and Respiratory Medicine
Citations in the corpus
- Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study (2019, result): “Reported adverse events in the present trial were generally acceptable and largely consistent with events previously reported by participants in the placebo arms of randomized controlled trials in IPF [45,46].”
- ANTIANGIOGENESIS STRATEGIES REVISITED: FROM STARVING TUMORS TO ALLEVIATING HYPOXIA (2014, positive): “…of desmoplasia by nintedanib, an AA agent that targets VEGFR, FGFR, and PDGF receptor (PDGFR) and proven to be effective in idiopathic pulmonary fibrosis, contributed to the survival benefit in combination with docetaxel in lung adenocarcinoma patients (Reck et al., 2014; Richeldi et al., 2014).”