Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis
Luca Richeldi,Roland M. du Bois,Ganesh Raghu,Arata Azuma,Kevin K. Brown,Ulrich Costabel,Vincent Cottin,Kevin R. Flaherty,David M. Hansell,Yoshikazu Inoue,Dong Soon Kim,Martin Kolb,Andrew G. Nicholson,Paul W. Noble,Moisés Selman,Hiroyuki Taniguchi,Michèle Brun,Florence Le Maulf,Mannaig Girard,Susanne Stowasser,Rozsa Schlenker-Herceg,Bernd Disse,Harold R. Collard +22 more
TLDR
In patients with idiopathic pulmonary fibrosis, nintedanib reduced the decline in FVC, which is consistent with a slowing of disease progression; nintinganib was frequently associated with diarrhea, which led to discontinuation of the study medication in less than 5% of patients.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.)read more
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Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline.
Ganesh Raghu,Martine Remy-Jardin,Jeffrey L. Myers,Luca Richeldi,Christopher J. Ryerson,David J. Lederer,Juergen Behr,Vincent Cottin,Sonye K. Danoff,Ferran Morell,Kevin R. Flaherty,Athol U. Wells,Fernando J. Martinez,Arata Azuma,Thomas Bice,Demosthenes Bouros,Kevin K. Brown,Harold R. Collard,Abhijit Duggal,Liam Galvin,Yoshikazu Inoue,R. Gisli Jenkins,Takeshi Johkoh,Ella A. Kazerooni,Masanori Kitaichi,Shandra L Knight,George Mansour,Andrew G. Nicholson,Sudhakar Pipavath,Ivette Buendía-Roldán,Moisés Selman,William D. Travis,Simon L.F. Walsh,Kevin C. Wilson +33 more
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Erik Sahai,Igor Astsaturov,Edna Cukierman,David G. DeNardo,Mikala Egeblad,Ronald M. Evans,Ronald M. Evans,Douglas T. Fearon,Douglas T. Fearon,Florian R. Greten,Sunil R. Hingorani,Tony Hunter,Richard O. Hynes,Rakesh K. Jain,Tobias Janowitz,Claus Jørgensen,Alec C. Kimmelman,Mikhail G. Kolonin,Robert G. Maki,Robert G. Maki,R. Scott Powers,Ellen Puré,Daniel C. Ramirez,Ruth Scherz-Shouval,Mara H. Sherman,Sheila A. Stewart,Thea D. Tlsty,David A. Tuveson,Fiona M. Watt,Valerie M. Weaver,Ashani T. Weeraratna,Zena Werb +31 more
TL;DR: This Consensus Statement issues a call to action for all cancer researchers to standardize assays and report metadata in studies of cancer-associated fibroblasts to advance the understanding of this important cell type in the tumour microenvironment.
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An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis. An Update of the 2011 Clinical Practice Guideline
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