Progressive fibrosing interstitial lung disease: a clinical cohort (the PROGRESS study)

Abstract

In patients with chronic fibrosing interstitial lung disease (ILD), a progressive fibrosing phenotype (PF-ILD) may develop, but information on the frequency and characteristics of this population outside clinical trials is lacking.We assessed the characteristics and outcomes of patients with PF-ILD other than idiopathic pulmonary fibrosis (IPF) in a real-world, single-centre clinical cohort. The files of all consecutive adult patients with fibrosing ILD (2010-2017) were examined retrospectively for pre-defined criteria of ≥10% fibrosis on high-resolution computed tomography and progressive disease during overlapping windows of 2 years. Baseline was defined as the date disease progression was identified. Patients receiving nintedanib or pirfenidone were censored from survival and progression analyses.In total, 1395 patients were screened; 617 had ILD other than IPF or combined pulmonary fibrosis and emphysema, and 168 had progressive fibrosing phenotypes. In 165 evaluable patients, median age was 61 years; 57% were female. Baseline mean forced vital capacity (FVC) was 74±22% predicted. Median duration of follow-up was 46.2 months. Annualised FVC decline during the first year was estimated at 136±328 mL using a linear mixed model. Overall survival was 83% at 3 years and 72% at 5 years. Using multivariate Cox regression analysis, mortality was significantly associated with relative FVC decline ≥10% in the previous 24 months (p<0.05), age ≥50 years (p<0.01) and diagnosis subgroup (p<0.01).In this cohort of patients with PF-ILD not receiving antifibrotic therapy, the disease followed a course characterised by continued decline in lung function, which predicted mortality.

Trial registration: ClinicalTrials.gov NCT03858842.

Conflict of interest statement

Conflict of interest: M. Nasser received sponsorship for conference attendance from Boehringer Ingelheim and Hoffmann-La Roche, and received consultation fees from Boehringer Ingelheim. Conflict of interest: S. Larrieu has nothing to disclose. Conflict of interest: S. Si-Mohamed has nothing to disclose. Conflict of interest: K. Ahmad reports relationships and activities from Roche and Boehringer Ingelheim, outside the submitted work. Conflict of interest: L. Boussel has nothing to disclose. Conflict of interest: M. Brevet has nothing to disclose. Conflict of interest: L. Chalabreysse has nothing to disclose. Conflict of interest: C. Fabre has nothing to disclose. Conflict of interest: S. Marque has nothing to disclose. Conflict of interest: D. Revel declares provision of scientific expertise under contract with IQVIA. Conflict of interest: F. Thivolet-Bejui has nothing to disclose. Conflict of interest: J. Traclet reports sponsorship for meeting attendance from Roche and Boehringer Ingelheim, outside the submitted work. Conflict of interest: S. Zeghmar has nothing to disclose. Conflict of interest: D. Maucort-Boulch has nothing to disclose. Conflict of interest: V. Cottin reports personal fees for advisory board work and lectures, and non-financial support for meeting attendance from Actelion, grants, personal fees for consultancy and lectures, and non-financial support for meeting attendance from Boehringer Ingelheim and Roche, personal fees for advisory board and data monitoring committee work from Bayer/MSD, personal fees for advisory board work and lectures from Novartis, personal fees for lectures from Sanofi, personal fees for data monitoring and steering committee work from Promedior, personal fees for data monitoring committee work from Celgene and Galecto, and personal fees for advisory board and data monitoring committee work from Galapagos, outside the submitted work.

Copyright ©ERS 2021.

Figures

FIGURE 1

Patient flowchart. IPF: idiopathic pulmonary fibrosis; CPFE: combined pulmonary fibrosis and emphysema; ILD: interstitial lung disease.

FIGURE 2

Linear mixed model estimation and 95% confidence intervals on raw forced vital capacity (FVC) (mL) associated with means (95% CI) of FVC (%) at calculated time points. For FVC decline, as the time intervals between measurements varied between subjects, time points were set at 12, 24, 36, 48, 60, 72 and 84 months, and FVC measurements were attributed to those time points using a ±6-month window, using the nearest measurement to the specific time point for analysis. Baseline number of patients at risk (n=135) indicates number of patients with values for pulmonary function tests. Change in FVC was analysed using a linear mixed model on raw measures and calculated time points, defined with a simple random-effect intercepts and slopes model with a fixed-effect intercept and a fixed-effect slope (β1), as well as a random-effect intercept (bi0) and random-effect slope (bi1), associated with an unstructured G-matrix covariance. The mixed model allowed estimates of FVC evolution, taking account of variability in both the number of measurements and time intervals between them.

FIGURE 3

Overall survival. a) Overall patient cohort; b) overall survival according to forced vital capacity (FVC) percentage at inclusion with a 70% threshold; c) overall survival according to Gender, Age and Physiology (GAP) index; d) overall survival according to disease subgroups. Survival estimates were performed using the Kaplan–Meier method in a) the overall population and b) patient subgroups by FVC decline, c) GAP index stage and d) disease subgroups compared by log-rank test. Baseline was defined as the date of disease progression. Patients were censored at the time of last clinic visit, lung transplantation for interstitial lung disease (ILD) or initiation of antifibrotic treatment. IIP: idiopathic interstitial pneumonia; HP: hypersensitivity pneumonitis.