P22 Progression patterns in nintedanib-treated individuals with progressive pulmonary fibrosis (PPF)

Introduction

Antifibrotic therapy with nintedanib has become the pharmacologic standard of care for patients with PPF. However, it remains unclear to what extent progression patterns of the underlying interstitial lung disease (ILD) or mortality may be altered by such treatment in practice.

Methods

A retrospective analysis of nintedanib-treated patients meeting INBUILD criteria for PPF (2018–2023) was undertaken. Baseline was defined as the date of lung function or computed tomography (CT) when criteria for PPF were met. Time-to-event analysis was performed using R Studio.

Results

322 patients [50.3% male; median age 69.5 (IQR 61–75)] were included. The commonest ILD subtypes were fibrotic hypersensitivity pneumonitis/FHP and connective tissue disease associated-ILD/CTD-ILD (121 each; 38%). In the overall cohort, ≥10% relative FVC decline was met by 146 (45.3%) patients whose risk of mortality was increased compared to patients (111/322; 34.5%) who met only radiological and symptomatic criteria for PPF [HR 1.88 (CI:1.30–2.73) (figure 1). Progression denoted by ≥15% relative decline in diffusion capacity/TLco and age >65 years at PPF diagnosis were also associated with higher mortality [HR 1.86 (CI:1.24–2.78)] and HR 1.48 (CI:1.19–1.83) respectively]. Compared with FHP, a CTD-ILD diagnosis was associated with a better prognosis [HR 0.65 (CI:0.44–0.97)]. Conversely, patients with unclassifiable ILD had a poorer outcome compared to those with FHP [HR 2.00 (CI:1.07–3.72)]. Nearly a fifth (59/322; 18%) of patients were unable to tolerate nintedanib due to adverse effects. 41 patients (12.7% of cohort) died within a year of satisfying PPF criteria. Patients with a relative decline in ≥10% FVC or ≥15% TLco or who could not complete gas transfer studies in these 12 months were at an increased risk of mortality [HR 3.34 (CI:1.75–6.38)]. A ≥10% relative FVC decline alone over that interval was associated with a higher risk of death [HR 2.82 (CI:1.57–5.07)]

Conclusions

Survival following satisfaction of PPF criteria varies depending on the progression pattern and the underlying disease. Progression defined by ≥10% relative FVC decline is associated with worse outcome both at baseline and if experienced as a subsequent event after commencing nintedanib therapy.