What is the initial management for fibrosing interstitial lung disease (ILD)?

Initial Management of Fibrosing Interstitial Lung Disease (ILD)

For patients with fibrosing interstitial lung disease, mycophenolate is conditionally recommended as the preferred first-line therapy across all systemic autoimmune rheumatic disease (SARD)-associated ILD subtypes. 1, 2

First-Line Treatment Options Based on Disease Type

For SARD-ILD (General Approach)

• Mycophenolate is the cornerstone first-line therapy for most SARD-ILD subtypes 1, 2
• Azathioprine is a conditionally recommended alternative first-line option for many SARD-ILD subtypes, except systemic sclerosis (SSc) 1, 2
• Rituximab and cyclophosphamide are conditionally recommended across all SARD-ILD subtypes 1, 2
• Glucocorticoids are conditionally recommended for SARD-ILD other than SSc-ILD 1
• For SSc-ILD, glucocorticoids are strongly recommended against due to risk of scleroderma renal crisis 1, 2

Disease-Specific First-Line Recommendations

• For SSc-ILD:

  • Tocilizumab and nintedanib are conditionally recommended as first-line options 1, 2
  • Mycophenolate remains a preferred option 1

• For idiopathic inflammatory myopathy (IIM)-ILD:

  • JAK inhibitors and calcineurin inhibitors (CNIs) are conditionally recommended as first-line options 1, 2
  • Mycophenolate is still a preferred option 1

• For rheumatoid arthritis (RA)-ILD:

  • No consensus exists on nintedanib as first-line therapy 1, 2
  • Mycophenolate, azathioprine, rituximab, and cyclophosphamide are conditionally recommended 1

• For progressive fibrosing ILD (PF-ILD):

  • Nintedanib is conditionally recommended, particularly for SSc-ILD 1, 3
  • Pirfenidone is conditionally recommended against as first-line treatment for SARD-ILD 1

Monitoring and Assessment of Progression

• Initial evaluation should include:

  • Short-term pulmonary function tests (PFTs) within 3 months 1
  • High-resolution computed tomography (HRCT) within 6 months 1

• Follow-up schedule:

  • For mild ILD (FVC ≥70% and <20% fibrosis on HRCT): PFTs every 6 months for first 1-2 years 1
  • For moderate-to-severe ILD or progressive disease: more frequent PFTs every 3-6 months 1
  • HRCT should be repeated within the first 3 years to identify progression 1

Management of Progressive Disease

If progression occurs despite first-line therapy:

• Mycophenolate, rituximab, cyclophosphamide, and nintedanib are conditionally recommended treatment options 1, 2
• For RA-ILD progression, adding pirfenidone is conditionally recommended 1, 2
• For SSc-ILD, MCTD-ILD, or RA-ILD progression, tocilizumab is conditionally recommended 1, 2
• For IIM-ILD progression, calcineurin inhibitors and JAK inhibitors are conditionally recommended 1, 2
• Long-term glucocorticoids are strongly recommended against in SSc-ILD and conditionally recommended against in other SARD-ILD subtypes 1

Antifibrotic Therapy Considerations

• Nintedanib:

  • Slows decline in forced vital capacity (FVC) in progressive fibrosing ILD 1, 3, 4
  • Common side effects include gastrointestinal symptoms, particularly diarrhea 5, 6
  • Conditionally recommended for SSc-ILD as first-line option 1

• Pirfenidone:

  • Conditionally recommended against as first-line treatment for SARD-ILD 1
  • May be considered for RA-ILD progression after first-line treatment 1
  • Common side effects include gastrointestinal symptoms and photosensitivity 7, 6

Common Pitfalls and Important Considerations

• Avoid glucocorticoids in SSc-ILD patients due to risk of scleroderma renal crisis, particularly at doses >15mg/day of prednisone equivalent 1, 2
• Early recognition of progressive disease is crucial as many forms of ILD can progress to irreversible fibrosis if not managed appropriately 1, 8
• Treatment decisions should consider disease subtype, severity, progression rate, and fibrotic pattern on imaging 1, 2
• A multidisciplinary approach involving pulmonologists, rheumatologists, radiologists, and pathologists improves diagnostic accuracy and likely improves outcomes 1
• Definition of progression (important for treatment decisions) includes:
  • Worsening symptoms
  • Decline in FVC (≥10% predicted or 5-10% with worsening symptoms)
  • Increased fibrosis on HRCT 1, 4