What are the treatment recommendations according to the 2025 Interstitial Lung Disease (ILD) classification?

2025 Interstitial Lung Disease (ILD) Classification and Treatment Recommendations

The 2025 ILD classification recommends mycophenolate mofetil as the preferred first-line treatment for most types of systemic autoimmune rheumatic disease-associated ILD (SARD-ILD), with specific recommendations tailored to disease subtypes. 1

First-Line Treatment Recommendations by ILD Subtype

Systemic Sclerosis-ILD (SSc-ILD)

• First-line options:
  • Mycophenolate (preferred) 2, 1
  • Nintedanib (conditionally recommended) 2
  • Tocilizumab (conditionally recommended) 2
• Avoid:
  • Glucocorticoids (strongly recommended against due to risk of scleroderma renal crisis) 2, 1
  • Pirfenidone (conditionally recommended against) 2
  • Dual combination therapy (conditionally recommended against) 2

Rheumatoid Arthritis-ILD (RA-ILD)

• First-line options:
  • Mycophenolate 2, 1
  • Rituximab 2
  • Azathioprine 2
  • Cyclophosphamide 2
• For progressive RA-ILD:
  • Pirfenidone may be added 2
  • Tocilizumab may be added 2
• Avoid:
  • Leflunomide, methotrexate, TNF inhibitors, abatacept 2, 1

Idiopathic Inflammatory Myopathy-ILD (IIM-ILD)

• First-line options:
  • Mycophenolate 2, 1
  • JAK inhibitors (particularly for anti-MDA-5 positive patients) 2, 1
  • Calcineurin inhibitors 2
  • Rituximab 2
  • Cyclophosphamide 2
• For progressive disease:
  • Adding calcineurin inhibitors is conditionally recommended 2

Sjögren's Disease-ILD (SjD-ILD)

• First-line options:
  • Mycophenolate 2
  • Rituximab 2
  • Azathioprine 2
  • Cyclophosphamide 2
• Avoid:
  • Nintedanib (conditionally recommended against) 2

Mixed Connective Tissue Disease-ILD (MCTD-ILD)

• First-line options:
  • Mycophenolate 2
  • Tocilizumab 2
  • Rituximab 2
  • Azathioprine 2
  • Cyclophosphamide 2
• Avoid:
  • Nintedanib (conditionally recommended against) 2

Management of Rapidly Progressive ILD

For rapidly progressive ILD (RP-ILD), more aggressive treatment is recommended:

• Initial therapy:

  • IV glucocorticoids (except in SSc-ILD where there's no consensus) 2
  • Plus 1-2 additional therapies from: 2
    • Rituximab
    • Cyclophosphamide
    • IVIG
    • Mycophenolate
    • Calcineurin inhibitors
    • JAK inhibitors

• For severe disease:

  • Two additional therapies from the above list 2
  • Consider early lung transplant referral 2, 1

• For confirmed/suspected MDA-5 RP-ILD:

  • Triple combination therapy over monotherapy 2

Monitoring Recommendations

• Pulmonary Function Tests (PFTs): 2, 3

  • For IIM-ILD and SSc-ILD: Every 3-6 months for the first year, then less frequently once stable
  • For RA-ILD, SjD-ILD, and MCTD-ILD: Every 3-12 months for the first year, then less frequently once stable
  • A 5% decline in FVC over 12 months is associated with approximately 2-fold increase in mortality

• High-Resolution CT (HRCT): 2, 1

  • No specific frequency guidance provided, but suggested when clinically indicated
  • Typically within the first 3 years after diagnosis and within 3-6 months to 1 year to determine treatment response

• Ambulatory desaturation testing: 2

  • Every 3-12 months

Treatment for Progressive Disease Despite First-Line Therapy

• For SARD-ILD progression after first-line therapy: 2
  • Add or switch to mycophenolate, rituximab, or cyclophosphamide
  • Consider adding nintedanib
  • For RA-ILD: Consider adding pirfenidone
  • For SSc-ILD, MCTD-ILD, RA-ILD: Consider adding tocilizumab
  • For IIM-ILD: Consider adding calcineurin inhibitors
  • Consider JAK inhibitors over azathioprine
  • Consider referral for stem cell transplantation and/or lung transplantation

Common Pitfalls to Avoid

• Delayed treatment initiation leading to irreversible fibrosis 1
• Inadequate monitoring resulting in undetected disease progression 1
• Inappropriate glucocorticoid use, particularly in SSc-ILD 2, 1
• Late referral for lung transplantation 1
• Using treatments specifically recommended against for certain ILD subtypes 2, 1
• Neglecting comorbidities such as GERD and pulmonary hypertension 1

The 2025 ILD classification emphasizes a tailored approach based on the specific SARD-ILD subtype, with mycophenolate as the preferred first-line agent for most subtypes, and specific recommendations for treatment escalation in progressive disease.