Meaningful Thresholds for Change in Quantitative CT-Derived Fibrosis Extent in Idiopathic Pulmonary Fibrosis

Validated thresholds for clinically meaningful change in quantitative CT (QCT) for fibrosis extent across algorithms remain unclear in idiopathic pulmonary fibrosis (IPF).

To evaluate minimal clinically important difference (MCID) for 1-year change in QCT metrics in IPF using different algorithms than previously reported, and to identify prognostically meaningful thresholds for effective risk stratification.

This multicenter retrospective study included IPF patients with baseline and 1-year follow-up CT. MCIDs for change in fibrosis score (ΔFS) derived from fully-automated CT quantification were estimated using an anchor-based approach with 1-year changes in forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLco), and a prognostic threshold was estimated using maximally selected log-rank statistics. Prognostic significance of ΔFS was evaluated in discovery and validation cohorts.

The discovery cohort included 524 patients (mean age, 66.8 years; 79% men), and the external validation cohort included 224 patients (mean age, 69.6 years; 83% men). Anchor-based MCIDs were 2.72% for FVC and 4.52% for DLco, with a prognostic threshold of 4.05%. In the discovery cohort, 1-year ΔFS were independently associated with transplant-free survival (TFS), with greater risk when ΔFS exceeded MCID or prognostic thresholds (all, P < .001). In the validation cohort, ΔFS remained associated with TFS (adjusted HR, 1.11; 95%CI, 1.04-1.18), and all prespecified ΔFS thresholds were prognostic for overall TFS, with the prognostic threshold of ΔFS ≥ 4.05% showing the most consistent associations with both overall (adjusted HR, 2.78; 95%CI, 1.36-5.68) and 3-year TFS (adjusted HR, 2.88; 95%CI, 1.11-7.48).

One-year change in FS and its thresholds were significantly associated with TFS, supporting annual CT follow-up with predefined QCT thresholds for monitoring and risk stratification in IPF.