Real-world impact of antifibrotics on prognosis in patients with progressive fibrosing interstitial lung disease

Abstract

Objective: No studies have demonstrated the real-world efficacy of antifibrotics for progressive fibrosing interstitial lung disease (PF-ILD). Therefore, we evaluated the efficacy of antifibrotics in patients with PF-ILD.

Methods: We retrospectively reviewed the medical records of patients with ILD from January 2012 to July 2021. Patients were diagnosed with PF-ILD if they had ≥10% fibrosis on high-resolution CT (HRCT) and a relative forced vital capacity (FVC) decline of either ≥10% or >5% to <10% with clinical deterioration or progression of fibrosis on HRCT during overlapping windows of 2 years and with a %FVC of ≥45%. We compared FVC changes and overall survival (OS) between patients with and without antifibrotics. FVC changes were analysed using generalised estimating equations. We used inverse probability weighting (IPW) and statistical matching to adjust for covariates.

Results: Of the 574 patients, 167 were diagnosed with PF-ILD (idiopathic pulmonary fibrosis (IPF), n=64; non-IPF, n=103). Antifibrotics improved the FVC decline in both IPF (p=0.002) and non-IPF (p=0.05) (IPW: IPF, p=0.015; non-IPF, p=0.031). Among patients with IPF, OS was longer in the antifibrotic group (log-rank p=0.001). However, among patients with non-IPF, OS was not longer in the antifibrotic group (p=0.3263) (IPW and statistical matching: IPF, p=0.0534 and p=0.0018; non-IPF, p=0.5663 and p=0.5618).

Conclusion: This is the first real-world study to show that antifibrotics improve the FVC decline in PF-ILD. However, among patients with non-IPF, we found no significant difference in mortality between those with and without antifibrotics. Future studies must clarify whether antifibrotics improve the prognosis of non-IPF.

Keywords: fibroblasts; pulmonary fibrosis; therapeutics.

Figure 1

Study design and patient population. *Patients were diagnosed with PF-ILD if they had ≥10% fibrosis on high-resolution CT (HRCT) and a relative forced vital capacity (FVC) decline of either ≥10% or >5% to <10% with clinical deterioration or progression of fibrosis on HRCT during overlapping windows of 2 years. CTD-ILD, connective tissue disease-related interstitial lung disease; HP, hypersensitivity pneumonitis; IIP, idiopathic interstitial pneumonia; IPAF, interstitial pneumonia with autoimmune features; IPF, idiopathic pulmonary fibrosis; PF-ILD, progressive fibrosing interstitial lung disease.

Figure 2

FVC change (mL) analysed by GEE at calculated time points in IPF and non-IPF. (A) Without adjustment. (B) With adjustment for multiple covariates^* using IPW. Each table shows a GEE analysis. Estimates and p values are shown for antifibrotics, month and the interaction between treatment and month. P values in bold indicate a significant effect. *Adjustment by age, sex, body mass index, FVC, glucocorticoid use (PSL at ≥10 mg/day), differential diagnoses (IPF, autoimmune ILD and lung-dominant ILD), and high-resolution CT findings (honeycombing and traction bronchiectasis). FVC, forced vital capacity; GEE, generalised estimating equation; IPF, idiopathic pulmonary fibrosis; IPW, inverse probability weighting; PF-ILD, progressive fibrosing interstitial lung disease; PSL, prednisolone.

Figure 3

Comparison of overall survival in antifibrotic group and no-antifibrotic group in IPF and non-IPF. (A) Without adjustment. (B) With adjustment for multiple covariates^* using IPW. *Adjustment by age, sex, body mass index, FVC, glucocorticoid use (PSL at ≥10 mg/day), differential diagnoses (IPF, autoimmune ILD and lung-dominant ILD) and high-resolution CT findings (honeycombing and traction bronchiectasis). FVC, forced vital capacity; IPF, idiopathic pulmonary fibrosis; IPW, inverse probability weighting; PF-ILD, progressive fibrosing interstitial lung disease; PSL, prednisolone.

Figure 4

Comparison of overall survival in antifibrotic group and no-antifibrotic group using propensity score matching for adjustment of multiple covariates*. *Adjustment by age, sex, body mass index, FVC, glucocorticoid use (PSL at ≥10 mg/day), differential diagnoses (IPF, autoimmune ILD and lung-dominant ILD) and high-resolution CT findings (honeycombing and traction bronchiectasis). FVC, forced vital capacity; IPF, idiopathic pulmonary fibrosis; PF-ILD, progressive fibrosing interstitial lung disease; PSL, prednisolone.