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

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Last updated: February 12, 2025View editorial policy

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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 progress over time in patients with RA-ILD 1
  • Pirfenidone's evidence is not sufficient due to the early termination of the TRAIL1 study, but it is still considered a therapeutic option for the management of progressive RA-ILD despite first-line treatment 1

Treatment Approach

  • The approach to treating RA-ILD is traditionally integrated and multidisciplinary, involving both rheumatologists and pulmonologists 1
  • Treatment with immunosuppressive agents is generally used regardless of the pattern of fibrosis, and patients are typically evaluated concurrently in a pulmonary and rheumatology consultation 1
  • The 2023 ACR guidelines conditionally recommend adding the anti-fibrotic treatment nintedanib or pirfenidone as therapeutic options for the management of progressive RA-ILD despite first-line treatment 1

Key Considerations

  • The clinical examination with auscultation are useful options for detecting Velcro-crackles, and risk factors must be considered to determine which patients are more likely to develop ILD 1
  • Short-term PFTs and HRCT should be considered to determine the rate of progression, and patients with moderate-to-severe ILD at baseline or progressive disease must have more frequent PFTs 1
  • The Patient Panel agreed to tolerate adverse effects for crucial treatments, but gastrointestinal adverse effects could significantly impact QoL 1

From the Research

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

  • There are several trials available for RA-ILD, including those investigating the efficacy of various medications such as mycophenolate, azathioprine, rituximab, and nintedanib 2, 3.
  • The Treatment for Rheumatoid Arthritis and Interstitial Lung Disease 1 (TRAIL1) trial is a randomized, double-blind, placebo-controlled, phase 2 study of the safety, tolerability, and efficacy of pirfenidone in patients with RA-ILD 4.

Medications Being Investigated

  • Janus kinase inhibitors (JAKi) have been shown to be effective in RA-ILD, with a pooled analysis demonstrating an increase in %pFVC and %pDLCO, as well as improvement in thoracic HRCT scans 5.
  • Nintedanib, an antifibrotic drug, has been suggested to be effective in patients with progressive lung fibrosis, including RA-ILD 3.
  • Pirfenidone is being investigated in the TRAIL1 trial, with the primary endpoint being the incidence of decline in percent predicted forced vital capacity or death during the 52-week study period 4.

Ongoing Research and Gaps in Knowledge

  • There is a substantial gap in RA-ILD treatment, with a need for more controlled trials to evaluate the effect of RA treatments on the ILD course 3.
  • International collaborative efforts are needed to address the lack of recommendations for screening high-risk patients and developing specific therapeutic strategies for RA-ILD 3.
  • Further research is needed to understand the pathogenesis, diagnosis, and treatment of RA-ILD, including the role of disease-modifying anti-rheumatic drugs (DMARDs) in preventing or worsening ILD 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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