Randomized, Double Blinded, Placebo-Controlled, Phase 2 Study of Safety, Tolerability and Efficacy of Pirfenidone in Patients with Rheumatoid Arthritis Interstitial Lung Disease

Abstract

Background: The TRAIL1 trial was a randomized, double-blinded, placebo-controlled, phase 2 study of safety, tolerability, and efficacy of pirfenidone for the treatment of patients with RA-ILD.

Methods: TRAIL1 was a phase 2 trial intended to enroll 270 adult patients with established RA-ILD. Patients were randomly assigned (1:1) to 2,403 mg oral pirfenidone or placebo. The primary endpoint was the incidence of the composite endpoint of decline from baseline in percent predicted FVC% of 10% or greater or death during the 52-week treatment period.

Findings: The difference in those who met the primary endpoint was not significant (11.1% on pirfenidone vs. 15% on placebo, [OR=0.67 (0.22, 2.03), p=0.48]). Subjects receiving pirfenidone had a slower rate of decline in lung function as measured by estimated annual change in FVC(ml) (-66 vs. -146, p=0.0082) and FVC(%) (-1.02 vs. -3.21, p=0.0028). This effect on decline was also seen when analyzed within participants with baseline usual interstitial pneumonia (UIP) pattern on HRCT (FVC(ml) (-43 vs. -169, p=0.0014) and FVC% (-0.2 vs. -3.81, p=0.0002)). There was no significant difference in the rate of treatment-emergent serious adverse events.

Interpretation: Due to early termination of the study, results should be interpreted with caution. Despite being underpowered to evaluate the primary endpoint, pirfenidone slowed the rate of decline of FVC over time in subjects with RA-ILD. Safety in patients with RA-ILD was similar to that seen in other pirfenidone trials.