A phase 2 trial that was terminated early still found that pirfenidone slowed the rate of decline of forced vital capacity (FVC) among patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD), according to results published in The Lancet Respiratory Medicine.
Interstitial lung disease is a known complication of rheumatoid arthritis. TRAIL1 (ClinicalTrials.gov Identifier: NCT02808871), a double-blind, randomized, placebo-controlled study, aimed to assess the efficacy, safety, and tolerability of pirfenidone for patients with RA-ILD.
The trial enrolled and randomized 123 patients from 34 academic centers specializing in ILD from May 2017 until March 2020, when the trial was stopped due to slow recruitment and the COVID-19 pandemic. Eligible participants were aged 18 to 85 years; met the 2010 American College of Rheumatology and European Alliance of Associations for Rheumatology criteria for rheumatoid arthritis; and were diagnosed with ILD via high-resolution computed tomography (CT) scan imaging as well as lung biopsy if available. Exclusion criteria included smoking, clinical history of other known causes of ILD, and coexistent clinically significant chronic obstructive pulmonary disease or asthma. Participants were divided into 2 groups, with 63 (51%) receiving 2403 mg oral pirfenidone daily and 60 (49%) receiving placebo.
The investigators found no significant difference between groups for the composite primary endpoint of a decline from baseline in percent predicted FVC of 10% or more or death during the 52-week treatment period (11% in the treatment group vs 15%, in the placebo group; odds ratio [OR], 0.67; 95% CI, 0.22-2.03; P =.48).
Patients in the treatment group had less annual change in absolute FVC (-66 vs -146; P =.0082) and percent predicted FVC (-1.02 vs -3.21; P =.0028). The analysis also found no significant difference in: (1) the number of participants from each group who experienced a decline in percent predicted FVC by 10% or more; (2) the frequency of progression as defined by Outcome Measures in Rheumatoid Arthritis Clinical Trials; and (3) the rate of treatment-emergent serious adverse events. There were no treatment-related deaths.
The study was limited by the its early termination, which may have precluded the observance of a safety or tolerability signal; selection bias due to the inclusion criteria of at least 10% fibrosis on high resolution CT; and a higher than usual number of patients with interstitial pneumonia in the placebo group. Additionally, only 12% of patients in the placebo group experienced a decline of 10% or more FVC over the 1-year study period, suggesting future trials should consider less stringent endpoints.
Researchers concluded, “Our study adds to the growing body of evidence that, similar to
studies in other subtypes of interstitial lung disease, we can identify patients with RA-ILD who have progressive fibrosis over time and benefit from antifibrotic therapy.”