Comparison of Pirfenidone and Nintedanib: Post-Hoc Analysis of the CleanUP-IPF Study.

Overview

abstract

BACKGROUND: Antifibrotics are effective in slowing forced vital capacity (FVC) decline in idiopathic pulmonary fibrosis (IPF). However, whether antifibrotic type is differentially associated with FVC decline remains inconclusive. RESEARCH QUESTION: Are there significant differences in 12-month FVC decline between pirfenidone and nintedanib? STUDY DESIGN AND METHODS: A post-hoc analysis was performed using CleanUP-IPF trial (NCT02759120). Participants who reported using pirfenidone or nintedanib upon enrollment into the trial were in the primary analysis. Spirometry was scheduled at baseline, 12-, and 24-month study visit. Linear mixed-effects models with random intercept and slope were used to examine changes in FVC over time. Models were adjusted for age, sex, smoking history, coronary artery disease history, baseline FVC, and 12-month spline term were used. Survival and non-elective respiratory hospitalization by antifibrotic type were determined using Cox regression models with adjustment for age, sex, smoking history, coronary artery disease history, and baseline FVC and diffusing capacity for carbon monoxide. RESULTS: Out of the 513 participants with IPF randomized in CleanUP-IPF, 407 reported using pirfenidone (n=264, 65%) or nintedanib (n=143, 35%). The pirfenidone group had more participants with a history of coronary artery disease than nintedanib (34.1% vs. 20.3%). Nintedanib-treated patients had a higher 12-month visit FVC compared with pirfenidone treated patients (mean difference 106 mL; 95% CI 34-178). This difference was attenuated at the 24-month study visit. There were no significant differences in overall survival and non-elective respiratory hospitalization between pirfenidone and nintedantib treated groups. INTERPRETATION: Patients with IPF who used nintedanib had a slower 12-month FVC decline than pirfenidone in a post-hoc analysis of a clinical trial.