Patients with rheumatoid arthritis and associated interstitial lung disease could be safely treated with pirfenidone, the TRAIL1 study showed. In participants receiving the antifibrotic, lung function decline was slowed down, particularly in those with a baseline usual interstitial pneumonia pattern.


Some patients with rheumatoid arthritis (RA) develop progressive fibrosing interstitial lung disease (ILD), characterized by increasing fibrosis on high-resolution computed tomography (HRCT), a decline in lung function, worsening symptoms, and high mortality. Patients with RA have a lifetime risk of 7.7% for this dreaded complication.1 Previously, nintedanib, an antifibrotic agent, has shown benefits in ILD associated with autoimmune disease. However, no completed treatment trials exclusively for RA subjects with ILD have previously been conducted. This was the rationale to perform the TRAIL1 trial (NCT02808871), a randomized, double-blinded, placebo-controlled, phase II study of tolerability and efficacy of the antifibrotic pirfenidone in patients with RA-associated ILD.2

All included patients had to have at least 10% fibrosis on HRCT but were not required to have documented progression. “The randomization 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) said. Therefore, only 123 patients could be randomized. Of them, 63 were treated with pirfenidone and 60 with placebo. The average extent of fibrosis was 20%.

Results showed that 11.1% of patients treated with pirfenidone achieved the primary endpoint—incidence of the composite of decline from baseline in percentage predicted force vital capacity (FVC%) of at least 10% or death during the 52-week treatment period—compared with 15% in the placebo group (OR, 0.67; P=0.48). Patients 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 (UIP) 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 had no new safety signals and slowed the decline of FVC over time in patients with RA-ILD. The beneficial effect was more pronounced in those with a UIP pattern on baseline HRCT.


  1. Bongartz T, et al. Arthritis Rheum. 2010 Jun;62(6):1583–
  2. 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– November.

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