Baylor College of Medicine

A partial cross-cut model of human lungs.

New drug potentially identified to expand rheumatoid arthritis-associated interstitial lung disease treatment

Aaron Nieto


Houston, TX -

The therapeutic drug pirfenidone has been found to be a potential treatment for rheumatoid arthritis-associated interstitial lung disease by researchers at Baylor College of Medicine, National Jewish Health and sites around the world.  

This complication of rheumatoid arthritis affects 7.7% of people diagnosed with the autoimmune disease that affects nearly 1% of the entire population. The findings appear in a recent issue of Lancet Respiratory Medicine.

“This is one of the first studies that has focused on treating patients with rheumatoid arthritis-associated interstitial lung disease,” said Dr. Ivan Rosas, corresponding author of the paper and professor of medicine and section chief of pulmonary, critical care and sleep medicine at Baylor College of Medicine.

Pirfenidone is classified as an anti-fibrotic medication that has shown effectiveness in treating patients with idiopathic pulmonary fibrosis. In 2014, the FDA approved the use of pirfenidone to treat this condition; however, its efficacy in treating rheumatoid arthritis-associated interstitial lung disease and other autoimmune conditions has not been previously tested. Although these are two distinct diseases, Rosas and other investigators have described similarities in their clinical appearance, outcomes and molecular signatures, prompting research with antifibrotic drugs.  

“Two out of every three patients with rheumatoid arthritis have features that closely resemble those of idiopathic pulmonary fibrosis,” Rosas said. “Clinically they look the same, in terms of their outcomes they behave the same and even their DNA markers look the same. Therefore, we thought, why not test this drug to see if it improves the health of those with rheumatoid arthritis-associated interstitial lung disease."

The Treatment for Rheumatoid Arthritis and Interstitial Lung Disease 1 (TRAIL1) study enrolled 123 patients from multiple clinical sites aged 18-85 who had evidence of fibrotic lung disease and who were not taking medication to treat this condition. Sixty-three of the patients received 2,403 mg of pirfenidone per day for one year and the remaining 60 patients received a placebo in the same timeframe.  

The TRAIL1 study was designed as a randomized, double-blind, placebo-controlled trial with the initial goal of enrolling a total of 254 patients. The study was terminated early due to low enrollment in part related to the COVID-19 pandemic. Despite only enrolling half of the projected participants, the study demonstrated a potential therapeutic effect.    

Although the study did not meet its primary endpoint, patients who took pirfenidone had a slower rate of decline in lung function, measured by estimated annual change in absolute forced vital capacity, the maximum amount of air you can forcibly exhale from your lungs after fully inhaling, compared to those who received a placebo. No new serious adverse events were reported, and nausea was the most common side effect patients experienced. Additionally, a subgroup of patients with rheumatoid arthritis-associated interstitial lung disease who had a significant decline in physiology and resembled idiopathic pulmonary fibrosis, was found to benefit the most from treatment with pirfenidone.

“Clinical trials with antifibrotic therapies have previously used an improvement in forced vital capacity as their primary endpoint. Because we were able to replicate this, we think this is clinically meaningful,” Rosas said.  

“This research is a big step forward for patients suffering from rheumatoid arthritis-associated interstitial lung disease,” said Dr. Joshua Solomon, director of the Interstitial Lung Disease Program at National Jewish Health and first author of the study.  

These findings will require independent validation and the design of a phase 3 study to receive FDA approval to treat rheumatoid arthritis-associated interstitial lung disease is being considered.

TRIAL1 was an international multicenter study, which was a randomized, double-blind, placebo-controlled, phase 2 trial done in 34 academic centers specializing in interstitial lung disease in four countries (U.K., U.S.A., Australia and Canada). Others who took part in this study include: Joshua J. Solomon, Sonye K. Danoff, Felix A. Woodhead, Shelley Hurwitz, Rie Maurer, Ian Glaspole, Paul F. Dellaripa, Bibek Gooptu, Robert Vassallo, P. Gerard Cox, Kevin R. Flaherty, Huzaifa I. Adamali, Michael A. Gibbons, Lauren Troy, Ian A. Forrest, Joseph A. Lasky, Lisa G. Spencer, Jeffrey Golden, Mary Beth Scholand, Nazia Chaudhuri, Mark A. Perrella, David A. Lynch, Daniel C. Chambers, Martin Kolb, Cathie Spino, Ganesh Raghu, Hilary J Goldberg and the TRAIL1 Network Investigators.  

For author affiliations, financial support and declaration of interests associated with this work, see the publication.

This study was funded by Genetech.

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