Frailty and functional outcomes in patients with progressive fibrosing interstitial lung diseases receiving antifibrotic therapy: a real-life observational study

Objectives: Treatment of idiopathic pulmonary fibrosis (IPF) and progressive fibrosing interstitial lung disease (PF-ILD) remain challenging in elderly patients with frailty, which negatively impact outcomes. This study aims at describing the prevalence of frailty in a cohort of patients with PF-ILD on antifibrotic therapy and to investigate its potential impact on treatment effectiveness and tolerability. Methods: This monocentric, retrospective study enrolled a total of 64 patients with either IPF or other progressive pulmonary fibrosis (PPF) treated with antifibrotic treatment at our center between June 2022 and November 2023. The frailty status of patients with ILD was measured using the Clinical Frailty Scale (CFS). Baseline data were used to classify patients into two groups according to CFS: (1) non-frail patients with CFS < 5 or (2) frail patients with CFS ≥ 5. Results: The mean CFS score in the overall population was 5.02 ± 1.62. Thirty-seven (58%) were frail while 27 (42%) met criteria for no-frailty. Frail patients, compared to non-frail, were older (74.4 ± 4.66 vs. 70.6 ± 4.78, p = 0.004), and had significantly lower FVC (L) (2.31 ± 0.75 L vs. 2.78 ± 0.75 L, p = 0.03), percent predicted DLco (%DLco) (43.47 ± 13.52 vs. 54.6 ± 11.48, p = 0.003) and lower 6-min walk distance (6MWD) (305 ± 159 vs. 410 ± 94, p = 0.006) compared to no-frail patients at baseline. Frail patients had higher ILD-GAP index (4.62 ± 1.41 vs. 3.88 ± 1.18, p = 0.037) compared to non-frail patients. Interestingly, functional trajectories decline was not significantly different between frail and no-frail patients. Regarding safety profile, medication dose reduction due to adverse events was greater in frail patients (51.3% vs. 26%, p = 0.04) while not significant differences emerged in side effects. Conclusion: Frailty has been associated with poorer lung function and greater physical impairment in patients with fibrotic ILDs under antifibrotic treatment. Frail patients also more frequently require medication dose reduction due to adverse effects.