Quantitative Computed Tomography in Progressive Pulmonary Fibrosis: Data from a Sub-Study of the Double Blind, Randomized, Placebo-controlled INBUILD Trial.

Abstract

Rationale: Change in forced vital capacity (FVC) is an established endpoint in clinical trials in lung fibrosis, but more sensitive measures of structural deterioration are needed. Quantitative computed tomography (QCT) measurements predict FVC decline and mortality, but more information is needed on their prognostic value and response to therapy.

Objectives: Evaluate the prognostic potential of quantitative CT measurements derived using University of California Los Angeles (UCLA) and e-Lung (Brainomix) algorithms, and effects of nintedanib on these measurements, in patients with progressive pulmonary fibrosis (PPF).

Methods: Among patients with PPF in a sub-study of the INBUILD trial (N = 474), associations between UCLA quantitative ILD and lung fibrosis (QILD and QLF) scores, e-Lung total disease extent (TDE), reticulovascular score (RVS), and weighted RVS, and ILD progression were assessed.

Measurements and main results: In the placebo group, higher baseline QCT scores were associated with a greater rate of decline in FVC (mL/year) over 52 weeks. The risk of decline in FVC % predicted ≥10% or death over 52 weeks was greater with QCT scores above vs below the median; differences in restricted mean survival time ranged from 40-65 days. Nintedanib had significant effects on changes in QILD score and e-Lung TDE at week 24 (relative difference versus placebo [%]: -7 [95% CI: -11, -2; p = 0.005] and -8 [-12, -4; p < 0.001], respectively) and week 52 (-7 [-12, -2; p < 0.05] for both).

Conclusions: Quantitative CT methods can facilitate prediction of progression and assessment of the efficacy of drugs in clinical trials in patients with PPF.