nintedanib and Acute-Disease

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.. 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.. 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%).. 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.. ClinicalTrials.gov NCT01335464 and NCT01335477 .

Topics: Acute Disease; Aged; Disease Progression; Enzyme Inhibitors; Female; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Male; Middle Aged; Severity of Illness Index; Vital Capacity

Time to first investigator-reported acute exacerbation was a key secondary end-point in the INPULSIS trials of nintedanib in patients with idiopathic pulmonary fibrosis (IPF).We used the INPULSIS trial data to investigate risk factors for acute exacerbation of IPF and to explore the impact of nintedanib on risk and outcome of investigator-reported and adjudicated confirmed/suspected acute exacerbations. Mortality following these events and events adjudicated as not acute exacerbations was analysed using the log rank test.Risk of acute exacerbations was most strongly associated with the following variables: baseline forced vital capacity (higher risk with lower value), baseline supplemental oxygen (higher risk with use), baseline antacid medication (higher risk with use), treatment (higher risk with placebo), and for confirmed/suspected acute exacerbations, cigarette smoking. Mortality was similar following investigator-reported and adjudicated confirmed/suspected acute exacerbations. Nintedanib had no significant effect on risk of mortality post-exacerbation.Investigator-reported acute exacerbations of IPF are associated with similar risk factors and outcomes as adjudicated confirmed/suspected acute exacerbations.

Topics: Acute Disease; Aged; Antacids; Cohort Studies; Disease Progression; Enzyme Inhibitors; Female; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Male; Middle Aged; Oxygen; Risk Factors; Smoking; Treatment Outcome; Vital Capacity

Topics: Acute Disease; Administration, Inhalation; Administration, Oral; Airway Remodeling; Airway Resistance; Animals; Anti-Asthmatic Agents; Asthma; Bronchi; Bronchoalveolar Lavage Fluid; Bronchoconstrictor Agents; Dexamethasone; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Glucocorticoids; Humans; Indoles; Inflammation Mediators; Methacholine Chloride; Mice; Ovalbumin

Topics: Acute Disease; Adrenal Cortex Hormones; Alveolitis, Extrinsic Allergic; Anti-Inflammatory Agents, Non-Steroidal; Antigens; Bronchoalveolar Lavage Fluid; Chronic Disease; Disease Progression; Enzyme Inhibitors; Humans; Immunoglobulin G; Immunologic Factors; Immunosuppressive Agents; Indoles; Lung; Lung Transplantation; Pyridones; Tomography, X-Ray Computed

Topics: Acute Disease; Enzyme Inhibitors; Glucocorticoids; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Pneumonia; Research Design