The therapeutic drug pirfenidone has been found as a potential treatment for interstitial lung disease associated with rheumatoid arthritis by researchers at Baylor College of Medicine, National Jewish Health and websites around the world.
Complications of rheumatoid arthritis affect 7.7% of people with an autoimmune disease that affects approximately 1% of the population. The results appear in a recent issue of Lancet Respiratory Medicine.
“This is one of the first studies to focus on treating patients with interstitial lung disease associated with rheumatoid arthritis.” Dr. Evan Rosasthe paper’s interview author and professor of medicine and chair of the division of pulmonology, critical care, and sleep medicine at Baylor College of Medicine.
Pirfenidone is classified as an antifibrotic drug that has been shown to be effective in treating patients with idiopathic pulmonary fibrosis. In 2014, the US Food and Drug Administration approved the use of pirfenidone to treat this condition. However, its effectiveness in treating interstitial lung disease associated with rheumatoid arthritis and other autoimmune conditions has not been tested. Although these are two different diseases, Rosas and other investigators have described similarities in their clinical appearance, findings, and molecular signatures, prompting the search for anti-fibrotic drugs.
“Two out of three patients with rheumatoid arthritis have features that are very similar to those of idiopathic pulmonary fibrosis,” Rosas said. “Clinically, they look similar, in terms of their results they act the same way and even their DNA markers look similar. So, we thought, why not test this drug to see if it improves the health of those with interstitial lung disease associated with rheumatoid arthritis.” “
The Treatment of Rheumatoid Arthritis and Interstitial Lung Disease 1 (TRAIL1) Study enrolled 123 patients from multiple clinical sites aged 18 to 85 years with evidence of fibrotic lung disease who were not taking medications for the condition. 63 patients received 2403 mg of pirfenidone daily for one year and 60 patients received placebo in the same time frame.
The TRAIL1 study was designed as a randomized, double-blind, placebo-controlled trial with the primary objective of enrolling a total of 254 patients. The study was terminated early due to low enrollment in part related to the COVID-19 pandemic. Although only half of the expected participants were enrolled, the study showed a potential therapeutic effect.
Although the study did not achieve the primary endpoint, patients who took pirfenidone had a slower rate of deterioration in lung function, measured by the estimated annual change in absolute forced vital capacity, which is the maximum amount of air you can force out of your lungs after inhalation. full. compared to those who received a placebo. No new serious adverse events were reported, and nausea was the most common side effect experienced by patients. In addition, a subgroup of patients with interstitial lung disease associated with rheumatoid arthritis who had a significant reduction in physiology and resembling idiopathic pulmonary fibrosis, was found to have the most benefit from treatment with pirfenidone.
Clinical trials with anti-inflammatory therapies have previously used an improvement in forced vital capacity as the primary end point. Because we were able to replicate this, we think this is clinically useful,” Rosas said.
“This research is a huge step forward for patients with interstitial lung disease associated with rheumatoid arthritis,” 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 consideration of a Phase III study design to receive FDA approval for the treatment of rheumatoid arthritis-associated interstitial lung disease.
TRIAL1 was an international, multicenter study that was a randomized, double-blind, placebo-controlled trial conducted at 34 academic centers specializing in interstitial lung disease in four countries (UK, USA, Australia and Canada). Others who participated in this study include: Joshua J. Solomon, Sonny K. Danoff, Felix A. Woodhead, Shelley Horowitz, Ray Maurer, Ian Glasspool, Paul F. Delariba, Bebek Gupto, Robert Vasallo, B. Gerard Cox, Kevin Flaherty, Hudifa A. Adamali, Michael A. Gibbons, Lauren Troy, Ian A. Forest, Joseph A. Lasky, Lisa J. Spencer, Jeffrey Golden, Mary Beth Chuland, Nazia Choudary, Mark A. Lynch, Daniel C. Chambers, Martin Kolb, Kathy Spino, Ganesh Raghu, Hilary J. Goldberg, and TRAIL1 network investigators.
For author affiliations, financial support, and declaration of interest associated with this work, see Publishing.
This study was funded by Genetech.