What trials are available for Rheumatoid Arthritis (RA) associated Interstitial Lung Disease (ILD)?

From the Guidelines

Rheumatoid Arthritis (RA) associated Interstitial Lung Disease (ILD) trials are limited, but available options include nintedanib and pirfenidone as anti-fibrotic therapies.

Available Trials

• Nintedanib has been shown to slow down disease progression in RA-ILD patients 1
• Pirfenidone's evidence is not sufficient due to the early termination of the TRAIL1 study 1

Treatment Approach

• The 2023 ACR guidelines conditionally recommend adding nintedanib or pirfenidone as therapeutic options for the management of progressive RA-ILD despite first-line treatment 1
• A multidisciplinary team approach is recommended for the management of RA-ILD, including rheumatologists and pulmonologists 1
• The treatment approach should be individualized, considering the balance between inflammatory and fibrotic ILD processes 1

Important Considerations

• Usual interstitial pneumonia (UIP) pattern in RA-ILD is associated with a poor prognosis and needs to be carefully evaluated 1
• Some disease-modifying anti-rheumatic drugs (DMARDs) have been recognized to be associated with an increased risk of lung toxicity, but the benefit/risk ratio is largely in favor of using them 1
• Glucocorticoids should be used with caution, and long-term use should be avoided due to the risk of adverse effects 1
• Immunosuppressive agents are generally used regardless of the pattern of fibrosis, and patients should be carefully evaluated for potential complications 1

From the Research

Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD) Trials

• There are several trials available for RA-ILD, including:
  • The TRAIL1 trial, a multicenter randomized, double-blind, placebo-controlled, phase 2 study of the safety, tolerability, and efficacy of pirfenidone in patients with RA-ILD 2
  • A large phase II trial exclusively in RA-ILD to evaluate the efficacy of antifibrotics in slowing the progression of ILD 3
• The 2023 American College of Rheumatology/American College of Chest Physicians guideline for ILD treatment in systemic autoimmune rheumatic diseases conditionally recommends mycophenolate, azathioprine, and rituximab for first-line RA-ILD therapy, with cyclophosphamide and short-term glucocorticoids as additional options 4
• Only three randomized controlled trials (RCTs) have enrolled patients with RA-ILD, highlighting the need for additional high-quality RCT data for efficacy and safety of anti-inflammatory and antifibrotic medications for RA-ILD 4

Ongoing Research and Gaps in Knowledge

• There is a substantial gap in RA-ILD treatment, notably evaluating the effect of RA treatments on the ILD course, due to a lack of controlled trials 5
• International collaborative efforts are needed to address the gaps in knowledge and develop specific recommendations for RA-ILD 5
• Clinical and translational research in RA-ILD is needed to fill the many evidence gaps, particularly in the management of RA-ILD 3

Current Treatment Options

• Antifibrotics, such as nintedanib, may be effective in patients with RA-ILD and the usual interstitial pneumonia pattern (RA-UIP) 4, 5
• Disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate, leflunomide, abatacept, and rituximab, may play beneficial roles in the prevention and treatment of RA-ILD 6