The University of Southampton
University of Southampton Institutional Repository

Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis

Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis
Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis
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.
2071-2082
Richeldi, Luca
47177d9c-731a-49a1-9cc6-4ac8f6bbbf26
du Bois, Roland M.
5f8aef36-d70e-4902-aded-f6da129c0741
Raghu, Ganesh
bf5d4a84-1eae-4e42-aac8-5fb9fb49d2ab
Azuma, Arata
f6ca02ae-75d2-4414-b4dd-ef74306a3e93
Brown, Kevin K.
3448c3ff-89a1-4cba-ab95-97bc178b6450
Costabel, Ulrich
4dc38723-49b2-4f71-aeee-6b959553c3b8
Cottin, Vincent
e73bdd1a-00d4-4cd2-9a0b-a796c361ca84
Flaherty, Kevin R.
9d1edc7b-124b-43b3-8d54-85f7b54b67ee
Hansell, David M.
69f8bbb1-4a39-43f1-aa6e-c5d49f7678cb
Inoue, Yoshikazu
deae4955-7f69-4fc2-a611-7f3fc07d09c4
Kim, Dong Soon
fc63af4d-dfe9-4131-9410-989dbc21a53e
Kolb, Martin
f7169cba-735d-4c03-b348-55f170d1b5dd
Nicholson, Andrew G.
96615ec5-6082-4999-b383-fca53d2f991b
Noble, Paul W.
ddf91f7c-f39e-4db3-b47f-2164bc293f8e
Selman, Moisés
42c44609-778c-4180-9ffc-fa913a68fbf8
Taniguchi, Hiroyuki
2ccfac1c-e5a4-4ac9-9683-1825867f1a1d
Brun, Michèle
6abe5e34-3d63-4d4e-b619-d510436e4c3c
Le Maulf, Florence
1b82bd53-2bc7-4a05-8116-a8091a030265
Girard, Mannaïg
5e003f44-562b-4ca6-87ce-21caa3de5a46
Stowasser, Susanne
db03e3f9-5df8-403d-b6f7-5284a506fd94
Schlenker-Herceg, Rozsa
b99d9236-8d93-43d8-8111-fa21b1f31e0b
Disse, Bernd
da210894-098a-40ba-bc5e-d0f658feadf5
Collard, Harold R.
6eee2ce5-3016-4c13-ac58-f30a77f7d141
Richeldi, Luca
47177d9c-731a-49a1-9cc6-4ac8f6bbbf26
du Bois, Roland M.
5f8aef36-d70e-4902-aded-f6da129c0741
Raghu, Ganesh
bf5d4a84-1eae-4e42-aac8-5fb9fb49d2ab
Azuma, Arata
f6ca02ae-75d2-4414-b4dd-ef74306a3e93
Brown, Kevin K.
3448c3ff-89a1-4cba-ab95-97bc178b6450
Costabel, Ulrich
4dc38723-49b2-4f71-aeee-6b959553c3b8
Cottin, Vincent
e73bdd1a-00d4-4cd2-9a0b-a796c361ca84
Flaherty, Kevin R.
9d1edc7b-124b-43b3-8d54-85f7b54b67ee
Hansell, David M.
69f8bbb1-4a39-43f1-aa6e-c5d49f7678cb
Inoue, Yoshikazu
deae4955-7f69-4fc2-a611-7f3fc07d09c4
Kim, Dong Soon
fc63af4d-dfe9-4131-9410-989dbc21a53e
Kolb, Martin
f7169cba-735d-4c03-b348-55f170d1b5dd
Nicholson, Andrew G.
96615ec5-6082-4999-b383-fca53d2f991b
Noble, Paul W.
ddf91f7c-f39e-4db3-b47f-2164bc293f8e
Selman, Moisés
42c44609-778c-4180-9ffc-fa913a68fbf8
Taniguchi, Hiroyuki
2ccfac1c-e5a4-4ac9-9683-1825867f1a1d
Brun, Michèle
6abe5e34-3d63-4d4e-b619-d510436e4c3c
Le Maulf, Florence
1b82bd53-2bc7-4a05-8116-a8091a030265
Girard, Mannaïg
5e003f44-562b-4ca6-87ce-21caa3de5a46
Stowasser, Susanne
db03e3f9-5df8-403d-b6f7-5284a506fd94
Schlenker-Herceg, Rozsa
b99d9236-8d93-43d8-8111-fa21b1f31e0b
Disse, Bernd
da210894-098a-40ba-bc5e-d0f658feadf5
Collard, Harold R.
6eee2ce5-3016-4c13-ac58-f30a77f7d141

Richeldi, Luca, du Bois, Roland M., Raghu, Ganesh, Azuma, Arata, Brown, Kevin K., Costabel, Ulrich, Cottin, Vincent, Flaherty, Kevin R., Hansell, David M., Inoue, Yoshikazu, Kim, Dong Soon, Kolb, Martin, Nicholson, Andrew G., Noble, Paul W., Selman, Moisés, Taniguchi, Hiroyuki, Brun, Michèle, Le Maulf, Florence, Girard, Mannaïg, Stowasser, Susanne, Schlenker-Herceg, Rozsa, Disse, Bernd and Collard, Harold R. (2014) Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. New England Journal of Medicine, 370 (22), 2071-2082. (doi:10.1056/NEJMoa1402584). (PMID:24836310)

Record type: Article

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.

This record has no associated files available for download.

More information

e-pub ahead of print date: 29 May 2014
Published date: 29 May 2014
Additional Information: Funded by Boehringer Ingelheim: INPULSIS-1 and INPULSIS-2 (ClinicalTrials.gov numbers, NCT01335464 and NCT01335477)
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 369051
URI: http://eprints.soton.ac.uk/id/eprint/369051
PURE UUID: 36ef9736-0509-4cdc-9a7f-ebdb920e2a85

Catalogue record

Date deposited: 24 Sep 2014 10:52
Last modified: 14 Mar 2024 17:57

Export record

Altmetrics

Contributors

Author: Luca Richeldi
Author: Roland M. du Bois
Author: Ganesh Raghu
Author: Arata Azuma
Author: Kevin K. Brown
Author: Ulrich Costabel
Author: Vincent Cottin
Author: Kevin R. Flaherty
Author: David M. Hansell
Author: Yoshikazu Inoue
Author: Dong Soon Kim
Author: Martin Kolb
Author: Andrew G. Nicholson
Author: Paul W. Noble
Author: Moisés Selman
Author: Hiroyuki Taniguchi
Author: Michèle Brun
Author: Florence Le Maulf
Author: Mannaïg Girard
Author: Susanne Stowasser
Author: Rozsa Schlenker-Herceg
Author: Bernd Disse
Author: Harold R. Collard

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×