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Differing severities of acute exacerbations of idiopathic pulmonary fibrosis (IPF): insights from the INPULSIS® trials.

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 .

SUBMITTER: Kreuter M

PROVIDER: S-EPMC6458653 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:The benefits and risks of anti-acid medication in patients with idiopathic pulmonary fibrosis (IPF) remain a topic of debate. We investigated whether use of anti-acid medication at baseline was associated with differences in the natural course of disease or influenced the treatment effect of nintedanib in patients with IPF. METHODS:Post-hoc analyses of outcomes in patients receiving versus not receiving anti-acid medication (proton pump or histamine-2 receptor inhibitor) at baseline using pooled data from the two Phase III randomized placebo-controlled INPULSIS® trials of nintedanib in patients with IPF. RESULTS:At baseline, 406 patients were receiving anti-acid medication (244 nintedanib; 162 placebo) and 655 were not (394 nintedanib; 261 placebo). In an analysis of the natural course of IPF by anti-acid medication use at baseline, the adjusted annual rate of decline in FVC was -?252.9 mL/year in placebo-treated patients who were receiving anti-acid medication at baseline and?-?205.4 mL/year in placebo-treated patients who were not (difference of -?47.5 mL/year [95% CI: -105.1, 10.1]; p?=?0.1057). In an analysis of the potential influence of anti-acid medication use on the treatment effect of nintedanib, the adjusted annual rates of decline in FVC were?-?124.4 mL/year in the nintedanib group and?-?252.9 mL/year in the placebo group (difference of 128.6 mL/year [95% CI: 74.9, 182.2]) in patients who were receiving anti-acid medication at baseline and?-?107.0 mL/year in the nintedanib group and?-?205.3 mL/year in the placebo group (difference of 98.3 mL/year [95% CI: 54.1, 142.5]) in patients who were not (treatment-by-time-by-subgroup interaction p?=?0.3869). The proportions of patients who had ?1 investigator-reported acute exacerbation were 11.7% and 5.0% in placebo-treated patients, and 4.9% and 4.8% of nintedanib-treated patients, among patients who were and were not receiving anti-acid medication at baseline, respectively. CONCLUSIONS:In post-hoc analyses of data from the INPULSIS® trials, anti-acid medication use at baseline was not associated with a more favorable course of disease, and did not impact the treatment effect of nintedanib, in patients with IPF. TRIAL REGISTRATION:ClinicalTrials.gov identifiers: NCT01335464 and NCT01335477 .

Project description:Background: An association between idiopathic pulmonary fibrosis (IPF) and advancing age is suspected since IPF occurs primarily in patients over 60 years of age. Though, little is known about the disease in the elderly. The aim of this study was to characterize elderly IPF patients using data from the longitudinal, German-wide INSIGHTS-IPF registry. Methods: Patients were grouped into elderly (≥75 years) and nonelderly IPF (<75 years) at the time of enrollment into the study. Baseline clinical characteristics, comorbidities, health related quality of life (HRQoL), medical therapy and survival were compared between age groups. Effects of antifibrotic therapy on forced vital capacity (FVC) were analyzed over 24 months. Results: Of 1,009 patients, 350 (34.7%) were ≥75 years old. Elderly IPF patients compared to younger patients had a higher number of comorbidities (3.6 ± 2.5 vs. 2.8 ± 2.3; p < 0.001). The mean ± SD EQ-5D score (0.64 ± 0.21 vs. 0.69 ± 0.21; p = 0.005), and the overall WHO-5 score (13.1 ± 5.9 vs. 14.3 ± 6.0; p = 0.015) were significantly lower while the UCSD-SOBQ (52.6 ± 31.2 vs. 45.5 ± 31.2; p = 0.030) was significantly higher in elderly patients, indicating a more impaired HRQoL and more breathlessness. At baseline, 55.4% of elderly and 56.8% of nonelderly patients with IPF were treated with antifibrotic therapy (p = 0.687). For FVC decline after initiation of antifibrotic therapy, there was neither a significant difference between age groups at the different time points over 24 months (beta: 0.41; 95%-CI: -0.98 to 1.81; p = 0.563) nor over the whole course of time (beta: -0.05; 95%-CI: -0.20 to 0.09; p = 0.478). All-cause mortality was higher in elderly patients (49.1 vs. 37.9%; HR 1.65; 95%-CI 1.36-2.00; p < 0.001). Antifibrotic therapy was associated with improved survival in IPF patients, independent from age (<75 years: beta 0.76; 95%-CI: 0.59-0.99; p = 0.049; ≥75 years: beta 0.71; 95%-CI: 0.51-0.98; p = 0.043). Conclusion: In real life, a significant proportion of IPF patients are ≥75 years old, characterized by higher number of comorbidities and global reduced HRQoL. However, the effect of an antifibrotic therapy was similar between age groups and associated with a survival benefit emphasizing the importance for an early antifibrotic therapy in IPF, independent from age.

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Differing severities of acute exacerbations of idiopathic pulmonary fibrosis (IPF): insights from the INPULSIS® trials.

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