Association of Antifibrotic Dosing Patterns With Clinical Outcomes in Patients With Idiopathic Pulmonary Fibrosis in Real-World Data Sources.

Abstract

Background: Antifibrotic therapies nintedanib and pirfenidone slow lung function decline in patients with idiopathic pulmonary fibrosis (IPF). However, both medications are often poorly tolerated, leading to dose reductions and discontinuations in practice.

Research question: How do antifibrotic dose changes (reductions or cessations) affect disease progression in IPF?

Study design and methods: This retrospective study analyzed data for patients with IPF who initiated antifibrotic therapy using two US data sources: the multicenter Pulmonary Fibrosis Foundation Patient Registry (Registry) and Duke University Health System electronic health records (EHR). Antifibrotic dose groups were defined as full dose, reduced dose for ≥3 months, or stopped therapy for ≥3 months. Associations between antifibrotic dose group, a time-varying exposure, and IPF progression, defined as composite ≥10% decline in ppFVC, all-cause hospitalization, lung transplant, or death, were analyzed by Cox proportional-hazards models adjusted for demographics and lung function.

Results: Over a median (25th/75th percentile) follow-up of 30.0 (17.5/30.0) months in the Registry and 14.0 (7.4/29.6) months in the EHR, 347/545 (63.7%) and 609/1,027 (59.3%) patients remained on full dose, respectively. Event rates for progression per 100 person-years in patients on full dose, reduced dose, or discontinuation were 39.74, 46.62, and 70.69, respectively, in the Registry and 44.82, 40.46, and 41.72 in the EHR. Time to progression did not differ significantly between patients who reduced or stopped antifibrotics and those who remained on full dose in the Registry (HR 1.17 [95% CI 0.90-1.52] for dose reduction, 1.51 [1.04-2.18] for discontinuation; P=.073) and EHR (HR 0.87 [0.69-1.09], 0.94 [0.66-1.36]; P=.476), respectively.

Interpretation: Among patients with IPF, antifibrotic dose reductions and discontinuations were common, likely due to poor drug tolerability. Disease progression occurred in a substantial proportion of patients in both cohorts, regardless of antifibrotic dosing strategy, highlighting the ongoing need for more effective and better-tolerated IPF therapies.