OBJECTIVES: Some patients with interstitial lung disease (ILD) develop a progressive fibrosing phenotype (PF-ILD) or progressive pulmonary fibrosis (PPF). Nintedanib has been shown in clinical trials to delay the progression of idiopathic pulmonary fibrosis (IPF) and non-IPF PPF. Whilst some studies have analyzed progression for up to 2 years in patients, little is known about progression in PPF past this timepoint. The objective of our analysis was to model disease progression or death over the lifetime of PPF patients.

METHODS: This analysis used data from patients with non-IPF PPF in the phase 3 INBUILD trial. Disease progression was defined as a ≥10% relative decline in forced vital capacity (FVC) within 12 months. Change in FVC was analyzed using regression analysis with independent models for nintedanib and placebo, plus a general model that included all patient data and a treatment coefficient. Survival analysis was conducted on the time-to-progression estimates from INBUILD as an alternative to the FVC regression analysis. The prediction of outcomes related to disease progression and mortality were simulated and expressed as time to disease progression using an individual patient-level simulation model.

RESULTS: The parameters in the regression models included baseline FVC, age, criteria for progressive ILD, acute exacerbation and interaction effects between time and fixed factors. All parameters were statistically significant at the 5% level with the exception of acute exacerbation. The incremental time to disease progression or death for nintedanib over placebo was 1.56 years using the independent models and 2.89 years using the general model. In the alternative time-to-progression analyses, the best fitting survival models were exponential, log-normal and Weibull, and the incremental time to disease progression or death ranged from 0.52 to 0.99 years.

CONCLUSIONS: This modelling suggested that nintedanib could delay long-term disease progression or death in patients with PPF.