Acute Exacerbations in Patients with Progressive Fibrosing Interstitial Lung Diseases: Data from the INBUILD Trial* 

Rationale Few data are available on acute exacerbations (A-EX) in patients with progressive fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF). Data from the INBUILD trial characterize A-EX in this population.

Methods Patients had diffuse fibrosing ILD (other than IPF) of>10% on HRCT, FVC≥45%, and DLco≥30%–<80% predicted, and criteria for progression of ILD within the prior 24 months, despite appropriate management in clinical practice. Patients were randomized to nintedanib or placebo. An A-EX of ILD was defined in the protocol as a clinically significant respiratory deterioration characterized by new, widespread alveolar abnormality meeting all these criteria: i) acute worsening or development of dyspnea (typically of<1 month duration); ii) CT with new bilateral ground-glass opacity or consolidation superimposed on a background pattern consistent with fibrosing ILD, iii) not fully explained by cardiac failure or fluid overload. Infection was not an exclusion criterion. A-EX were reported by investigators as part of the pre-specified reporting of adverse events and were not adjudicated. We compared the baseline characteristics of patients who did versus did not have an A-EX during the trial (both groups pooled) and analyzed the times from A-EX to hospitalization and death ([Abb. 1]).

Abb. 1  Time from first acute exacerbation of ILD to i) hospitalization and ii)deaht in patents with progressive fibrosing ILDS in the INBUILD trial.

Results A-EX were reported in 58 of 663 (8.7%) patients during the follow-up (median: approximately 19 months). Of these, 18 (31.0%) had hypersensitivity pneumonitis, 15 (25.9%) unclassifiable idiopathic interstitial pneumonia, 12 (20.7%) an autoimmune disease-related ILD, 6 (10.3%) idiopathic non-specific interstitial pneumonia, and 7 (12.1%) other ILDs. Compared with the patients who did not have anA-EX, the patients who had an A-EX included a greater proportion of males (65.5% vs 52.6%), current or former smokers (53.4% vs 50.7%), and patients with a usual interstitial pneumonia (UIP)-like fibrotic pattern on HRCT (65.5% vs 61.8%) and had a lower FVC (65.7% vs 69.3% predicted) and lower DLco (40.7% vs 46.6% predicted) at baseline. Kaplan-Meier estimates of rates of hospitalization and death within 180 days of an A-EX were 90.6% and 37.0%, respectively (Figure).

Conclusions The INBUILD trial suggest that in patients with PF-ILDs other than IPF, A-EX are associated with a high risk of hospitalization and death.

Publication History

Article published online:
09 March 2023