What is the treatment approach for interstitial lung disease (ILD)?

Treatment Approach for Interstitial Lung Disease (ILD)

The treatment of interstitial lung disease should be tailored to the specific ILD subtype, with mycophenolate being the preferred first-line agent for most systemic autoimmune rheumatic disease-associated ILD (SARD-ILD), while antifibrotic medications are recommended for idiopathic pulmonary fibrosis. 1

Treatment Based on ILD Subtype

Systemic Autoimmune Rheumatic Disease-Associated ILD (SARD-ILD)

First-line Treatment Options:

1. Mycophenolate - Conditionally recommended as the preferred first-line agent for all SARD-ILD subtypes 1
2. Glucocorticoids:
   • Conditionally recommended for SARD-ILD other than systemic sclerosis (SSc-ILD) 1
   • Strongly recommended against for SSc-ILD 1
3. Other first-line options (conditionally recommended):
   • Azathioprine
   • Rituximab
   • Cyclophosphamide 1

Disease-Specific First-line Recommendations:

• SSc-ILD and Mixed Connective Tissue Disease (MCTD-ILD):

  • Tocilizumab (conditionally recommended) 1
  • Nintedanib (conditionally recommended for SSc-ILD only) 1

• Inflammatory Myopathy-associated ILD (IIM-ILD):

  • JAK inhibitors (conditionally recommended) 1
  • Calcineurin inhibitors (conditionally recommended) 1

Treatments Conditionally Recommended Against:

• Leflunomide
• Methotrexate
• TNF inhibitors
• Abatacept
• Pirfenidone 1

Idiopathic Pulmonary Fibrosis (IPF)

• Antifibrotic therapy with nintedanib or pirfenidone is the cornerstone of treatment 2
  • Slows annual FVC decline by approximately 44% to 57% 2
  • Should be prescribed according to American Thoracic Society/European Respiratory Society Guidelines 1

Management of Progressive ILD

For SARD-ILD Progression Despite First-line Treatment:

1. Conditionally recommended options:

   • Mycophenolate
   • Rituximab
   • Cyclophosphamide
   • Nintedanib 1

2. Disease-specific second-line options:

   • RA-ILD: Consider adding pirfenidone 1
   • SSc-ILD, MCTD-ILD, RA-ILD: Consider tocilizumab 1
   • IIM-ILD: Consider calcineurin inhibitors, JAK inhibitors, or IVIG 1

3. For SSc-ILD with progression: Consider referral for stem cell transplantation and/or lung transplantation 1

Management of Rapidly Progressive ILD (RP-ILD)

1. First-line treatment:

   • Pulse intravenous methylprednisolone (conditionally recommended) 1
   • Upfront combination therapy is preferred over monotherapy 1
     • Triple therapy for those with confirmed/suspected MDA-5
     • Double/triple therapy for others

2. Conditionally recommended agents:

   • Rituximab
   • Cyclophosphamide
   • IVIG
   • Mycophenolate
   • Calcineurin inhibitors
   • JAK inhibitors 1

3. Early referral for lung transplantation is conditionally recommended 1

Supportive Care and Symptom Management

1. Cough management:

   • Evaluate for other causes (asthma, GERD, upper airway cough syndrome) 1
   • For IPF-associated cough, antifibrotic therapy may reduce severity 1

2. Exercise and rehabilitation:

   • Structured exercise therapy reduces symptoms and improves 6-minute walk test distance 2

3. Oxygen therapy:

   • Recommended for patients who desaturate below 88% on a 6-minute walk test 2
   • Reduces symptoms and improves quality of life 2

4. Management of pulmonary hypertension:

   • Up to 85% of individuals with end-stage fibrotic ILD develop pulmonary hypertension 2
   • Inhaled treprostinil can improve walking distance and respiratory symptoms 2

Monitoring Disease Progression

• Regular assessment of pulmonary function tests (PFTs)
• A 5% decline in FVC over 12 months is associated with approximately 2-fold increase in mortality 2
• Consider lung transplant for patients with advanced ILD 2

Common Pitfalls and Caveats

1. Avoid glucocorticoids in SSc-ILD - Strongly recommended against due to risk of renal crisis 1

2. Don't delay treatment escalation - Progressive disease requires prompt intervention to prevent irreversible fibrosis

3. Consider comorbidities - Address GERD, pulmonary hypertension, and other conditions that may exacerbate ILD

4. Recognize rapidly progressive disease - Requires aggressive combination therapy and early consideration for lung transplantation 1

5. Don't miss treatable causes - Always consider hypersensitivity pneumonitis, drug-induced ILD, and other potentially reversible causes 3