eprintid: 26339
rev_number: 14
eprint_status: archive
userid: 1589
dir: disk0/00/02/63/39
datestamp: 2019-06-17 09:09:28
lastmod: 2019-07-11 11:41:40
status_changed: 2019-06-17 09:09:28
type: article
metadata_visibility: show
creators_name: Kreuter, Michael
creators_name: Koegler, Harald
creators_name: Trampisch, Matthias
creators_name: Geier, Silke
creators_name: Richeldi, Luca
title: Differing severities of acute exacerbations of idiopathic pulmonary fibrosis (IPF): insights from the INPULSIS® trials
subjects: ddc-610
divisions: i-950900
keywords: Nintedanib, Tyrosine kinase inhibitor, Serious adverse events, Disease progression, Treatment outcome
abstract: Background: Given the broad definition of an acute exacerbation of IPF, it is likely that acute exacerbations are heterogeneous in their aetiology, severity and clinical course. We used pooled data from the INPULSIS® trials of nintedanib versus placebo to investigate whether acute exacerbations reported as serious adverse events were associated with higher mortality than those reported as non-serious adverse events and to assess the effect of nintedanib on these types of events.

Methods: Adverse events considered by an investigator to be an acute exacerbation were adjudicated as a confirmed acute exacerbation, suspected acute exacerbation, or not an acute exacerbation. Time to first investigator-reported acute exacerbation or confirmed/suspected acute exacerbation reported as a serious adverse event or non-serious adverse event over the 52-week treatment period was assessed post-hoc. Deaths were assessed based on data collected over the 52-week treatment period.

Results: Of 63 patients who had ≥1 investigator-reported acute exacerbation, 48 (76.2%) had a first acute exacerbation reported as a serious adverse event. Thirty-six (3.4%) patients had ≥1 confirmed/suspected acute exacerbation, of whom 31 had a first event reported as a serious adverse event. Investigator-reported acute exacerbations reported as serious adverse events occurred in 23 patients in the nintedanib group and 26 in the placebo group. Confirmed/suspected acute exacerbations reported as serious adverse events occurred in 10 and 21 patients in these groups, respectively. Nintedanib significantly reduced the risk of a first acute exacerbation reported as a serious adverse event (HR 0.57 [95% CI: 0.32, 0.99]; p = 0.0476) and the risk of a first confirmed/suspected acute exacerbation reported as a serious adverse event (HR 0.30 [95% CI: 0.14, 0.64]; p = 0.0019) versus placebo. A higher proportion of patients with investigator-reported acute exacerbations reported as serious adverse events died than patients with acute exacerbations reported as non-serious adverse events (61.2% versus 7.1%).

Conclusion: Different severities of acute exacerbation of IPF may exist. Acute exacerbations reported as serious adverse events in the INPULSIS® trials were associated with high mortality. Nintedanib significantly reduced the risk of acute exacerbations reported as serious adverse events.

Trial registration: ClinicalTrials.gov, NCT01335464 and NCT01335477.
date: 2019
publisher: BioMed Central
id_scheme: DOI
ppn_swb: 1667615084
own_urn: urn:nbn:de:bsz:16-heidok-263392
language: eng
bibsort: KREUTERMICDIFFERINGS2019
full_text_status: public
publication: Respiratory Research
volume: 20
number: 71
place_of_pub: London
pagerange: 1-7
issn: 1465-993X
citation:   Kreuter, Michael ; Koegler, Harald ; Trampisch, Matthias ; Geier, Silke ; Richeldi, Luca  (2019) Differing severities of acute exacerbations of idiopathic pulmonary fibrosis (IPF): insights from the INPULSIS® trials.  Respiratory Research, 20 (71).  pp. 1-7.  ISSN 1465-993X     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/26339/1/12931_2019_Article_1037.pdf