The TRAIL1 study is the first trial to demonstrate the efficacy and safety of pirfenidone in patients with rheumatoid arthritis (RA) and associated interstitial lung disease (ILD). In participants receiving the antifibrotic, lung function decline was slowed down, particularly in those with a usual interstitial pneumonia pattern at baseline.
Some patients with RA develop progressive fibrosing ILD, characterised by increasing fibrosis on high-resolution CT, a decline in lung function, worsening symptoms, and high mortality. Patients with RA have a lifetime risk of 7.7% for this complication, which is an 8-time higher relative risk to develop ILD compared with the general population . Previously, the antifibrotic agent nintedanib has shown benefits in patients with autoimmune-associated ILD . Up to now, no completed treatment trials exclusively for RA subjects with ILD exist. This was the rationale to perform the TRAIL1 (NCT02808871), a randomised, double-blinded, placebo-controlled, phase 2 study of tolerability and efficacy of the antifibrotic pirfenidone in patients with RA-associated ILD .
All included patients had to have ≥10% fibrosis on high-resolution CT but were not required to have documented progression. “The randomisation target was 270 participants, but the study was stopped due to slow recruitment exacerbated by the COVID-19 pandemic,” Prof. Joshua J. Solomon (National Jewish Health, CO, USA) said. Therefore, only 123 patients were randomised. Of these, 63 were treated with pirfenidone and 60 with placebo. The average extent of fibrosis was 20%. The primary endpoint was the incidence of a composite of decline from baseline in percentage predicted force vital capacity (FVC%) of ≥10% or death during the 52-week treatment period.
Results showed that 11.1% of patients treated with pirfenidone achieved the primary endpoint compared with 15% in the placebo group (OR 0.67; P=0.48). Subjects treated with pirfenidone had a slower rate of decline in lung function, measured by estimated annual change in FVC. This benefit was particularly seen in participants with a baseline usual interstitial pneumonia pattern on HRCT. There was no significant difference in the rate of treatment-emergent serious adverse events.
Prof. Solomon concluded that although the trial was underpowered to detect a difference in the composite primary endpoint, pirfenidone showed no new safety signals and slowed the decline of FVC over time in subjects with RA-ILD. The beneficial effect was more pronounced in those with a usual interstitial pneumonia pattern on baseline HRCT.
- Bongartz T, et al. Arthritis Rheum. 2010 Jun;62(6):1583–91.
- Flaherty KR, et al. New Engl J Med 2019;381:1718-27.
- Solomon JJ, et al. A randomized, double-blinded, placebo-controlled, phase 2 study of safety, tolerability and efficacy of pirfenidone in patients with rheumatoid arthritis interstitial lung disease. Abstract L10. ACR Convergence 2021, 3–10 November.
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Table of Contents: ACR 2021
Letter from the Editor
ACR 2021 Highlights Podcast
Vaccine booster improves immune response in patients treated with rituximab
IL-17 inhibition showing efficacy in GCA in phase 2 trials
Spotlight on Rheumatoid Arthritis
Cycling JAK inhibitors shows similar effectiveness to switching to a bDMARD in difficult-to-treat RA
Pre-existing heart failure affects safety of hydroxychloroquine in RA patients
Patients with RA-associated interstitial lung disease benefit from antifibrotic agent
Ultra-low dosing of rituximab in RA is a viable treatment option
Kidney disease and hydroxychloroquine dose are risk factors for developing retinopathy
More pros than cons for the use of statins in RA
Psoriatic Arthritis: Novel Developments
Selective IL-23 inhibition: a new option in active PsA
Ustekinumab: highly efficacious in PSA independent of methotrexate
COVID-19: What You Need to Know
Vaccinated rheumatic patients carry increased risk for COVID-19 breakthrough infections
B-cell depleting medication increases COVID-19 breakthrough infection outcome risk
COVID-19 mRNA vaccine safe and tolerable in adults with autoimmune disease
SLE Treatment: What Is New
Iberdomide: an upcoming new treatment possibility in lupus erythematosus
Sequential rituximab after belimumab does not improve disease control in SLE
Lupus patients less protected by COVID-19 vaccine
Promising results in uric acid-lowering in gout patients with a new xanthine oxidase inhibitor
Laboratory and clinical signs 24h after hospitalisation predict MIS-C in children
Knee & Hip Osteoarthritis: More Alike Than Different