Should nintedanib (antifibrotic agent) be started during an acute Interstitial Lung Disease (ILD) exacerbation?

Nintedanib During Acute ILD Exacerbation

Nintedanib should not be initiated during an acute exacerbation of interstitial lung disease (ILD), as current guidelines recommend stabilizing the acute event with immunosuppressive therapy first before considering antifibrotic agents. 1

Current Guideline Recommendations

The 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guidelines make several recommendations regarding nintedanib in ILD treatment:

• For people with systemic sclerosis-associated ILD (SSc-ILD), nintedanib is conditionally recommended as a first-line ILD treatment option 1
• For people with Sjögren's disease-ILD (SjD-ILD), inflammatory myopathy-ILD (IIM-ILD), and mixed connective tissue disease-ILD (MCTD-ILD), nintedanib is conditionally recommended against as a first-line ILD treatment option 1
• For rheumatoid arthritis-ILD (RA-ILD), the expert panel could not reach consensus on recommending nintedanib as a first-line treatment 1

Management of Acute ILD Exacerbation

Acute exacerbations of ILD represent sudden deteriorations in respiratory function and require prompt intervention. The guidelines suggest:

1. First-line approach: For acute ILD exacerbations, particularly in systemic autoimmune rheumatic disease-associated ILD (SARD-ILD) other than SSc-ILD, glucocorticoids are conditionally recommended as initial treatment 1

2. Timing of nintedanib: The guidelines recommend nintedanib primarily for progressive fibrosing disease, not during acute exacerbations 1

3. Sequential approach: Guidelines conditionally recommend against adding nintedanib to immunosuppressive therapy (like mycophenolate) without evidence of ILD progression 1

Emerging Research vs. Guidelines

Despite the guideline recommendations, some emerging research suggests potential benefits of nintedanib during acute exacerbations:

• A 2022 Japanese database study found that nintedanib initiation during acute exacerbation was associated with lower in-hospital mortality (OR 0.43) and shorter hospitalization in patients with fibrosing ILDs 2

• A case report described improvement in a patient with acute exacerbation of ILD treated with nintedanib alone 3

However, these findings must be interpreted with caution as they contradict current guideline recommendations and have not been incorporated into clinical practice guidelines.

Practical Approach to Acute ILD Exacerbation

1. Stabilize the acute event first:

   • Use glucocorticoids as recommended for acute management 1
   • Consider other immunosuppressive agents based on the underlying ILD type

2. After stabilization:

   • Consider nintedanib for patients with progressive fibrosing ILD, particularly in SSc-ILD 1
   • For other SARD-ILDs, immunosuppressive therapies are generally preferred as first-line options 1

3. Monitor for progression:

   • Regular assessment of symptoms and oxygen saturation
   • Pulmonary function tests every 3-6 months
   • HRCT if unexplained clinical changes occur 4

Cautions and Considerations

• Nintedanib primarily slows FVC decline rather than providing stabilization or improvement 1
• Common adverse effects include diarrhea, which can significantly impact quality of life 1, 5
• Cost considerations may limit accessibility 1, 6
• Nintedanib requires regular monitoring, including monthly liver function tests for the first 6 months 4

In conclusion, while emerging research suggests potential benefits, current guidelines do not support initiating nintedanib during an acute ILD exacerbation. The standard approach remains to stabilize the acute event first with appropriate immunosuppressive therapy before considering antifibrotic agents like nintedanib for long-term management of progressive disease.