Abstract
BackgroundGiven 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.MethodsAdverse 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.ResultsOf 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%).ConclusionDifferent 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 registrationClinicalTrials.govNCT01335464 and NCT01335477.
Highlights
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrosing interstitial lung disease characterised by loss of lung function [1]
We used data from the Phase III INPULSIS® trials of nintedanib in patients with IPF to investigate whether acute exacerbations reported as serious adverse events were associated with higher mortality than events reported as non-serious adverse events and to assess the effect of nintedanib on these events
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) (Fig. 2)
Summary
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrosing interstitial lung disease characterised by loss of lung function [1]. Many patients experience acute deteriorations in lung function known as acute exacerbations, which are associated with very high morbidity and mortality [3]. A perspective published by an international group of experts in 2007 defined acute exacerbations of IPF as acute deteriorations in respiratory symptoms associated with changes in radiographical appearance and the absence of an identifiable cause [4]. In clinical trials conducted in patients with IPF and mild to moderate impairment in lung function at baseline, acute exacerbations were reported in 2 to 16% of placebo-treated patients over 24 to 60 weeks [5,6,7,8,9,10,11,12,13,14,15,16,17]. 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
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