What is the treatment approach for Interstitial Lung Disease (ILD)?

Treatment Approach for Interstitial Lung Disease (ILD)

Mycophenolate mofetil is the preferred first-line treatment for most forms of systemic autoimmune rheumatic disease-associated ILD (SARD-ILD), with treatment selection varying based on the specific underlying disease and disease severity. 1, 2

First-Line Treatment Options by ILD Type

General Approach to SARD-ILD

• Preferred first-line agent: Mycophenolate mofetil (1000-1500 mg twice daily) 1, 2
• Alternative first-line options:
  • Rituximab (especially for RA-ILD with active inflammatory arthritis)
  • Azathioprine
  • Cyclophosphamide (for severe disease)
  • Nintedanib (especially for progressive fibrosing phenotype) 2, 3

Disease-Specific Considerations

Systemic Sclerosis-ILD (SSc-ILD)

• Strongly recommended against: Long-term glucocorticoids (risk of scleroderma renal crisis) 1
• Preferred options:
  • Mycophenolate mofetil
  • Nintedanib (FDA-approved for SSc-ILD)
  • Tocilizumab (for progressive disease) 1, 2

Inflammatory Myopathy-ILD (IIM-ILD)

• Preferred options:
  • Mycophenolate mofetil
  • Calcineurin inhibitors (tacrolimus preferred over cyclosporine)
  • Rituximab 1
• For MDA-5 positive patients: Consider upfront combination therapy 1

Rheumatoid Arthritis-ILD (RA-ILD)

• Preferred options:
  • Mycophenolate mofetil
  • Rituximab (especially with active joint disease)
  • Tocilizumab 1, 2
• Avoid: Methotrexate, leflunomide, TNF inhibitors 1, 2

Glucocorticoid Use in ILD

• Short-term use only: Oral prednisone 0.5-1 mg/kg/day (maximum 60 mg/day) with taper to ≤10 mg/day over 3 months 2
• For acute presentations: IV pulse methylprednisolone (1000 mg IV for 3 days) may be beneficial 4
• Strong recommendation against: Long-term glucocorticoids in SSc-ILD 1
• Conditional recommendation against: Long-term glucocorticoids in other SARD-ILD 1

Management of Progressive Disease

If disease progresses despite first-line therapy (defined as >5% decline in FVC over 12 months):

1. For SSc-ILD progression:

   • Consider nintedanib
   • Referral for stem cell transplantation or lung transplantation 1

2. For IIM-ILD progression:

   • Add or switch to JAK inhibitors
   • Consider IVIG (especially with respiratory muscle weakness)
   • Consider calcineurin inhibitors 1

3. For RA-ILD progression:

   • Consider rituximab if not already used
   • Consider nintedanib for progressive fibrosing phenotype 1, 3

Rapidly Progressive ILD (RP-ILD)

For rapidly progressive ILD, which carries substantial mortality risk:

• First-line treatment: Pulse IV methylprednisolone 1
• Combination therapy recommended: Triple therapy for MDA-5 positive patients; double or triple therapy for others 1
• Preferred agents:
  • Rituximab
  • Cyclophosphamide
  • IVIG
  • Mycophenolate
  • Calcineurin inhibitors (for IIM-ILD)
  • JAK inhibitors (for IIM-ILD) 1
• Early referral: For lung transplantation evaluation 1, 2

Monitoring and Follow-up

• Regular PFTs: Every 3-6 months to assess for disease progression 2
• HRCT: At baseline and as clinically indicated 2
• Medication monitoring: Follow specific monitoring guidelines for each agent (see table in guideline) 1
• Key threshold: A 5% decline in FVC over 12 months is associated with approximately 2-fold increase in mortality 3

Supportive Care

• Oxygen therapy: For patients who desaturate below 88% on a 6-minute walk test 2, 3
• Exercise rehabilitation: Structured exercise therapy improves symptoms and 6-minute walk test distance 3
• Cough management: Evaluate for other causes (GERD, asthma) 2

Important Caveats

• The treatment approach should be co-managed by rheumatologists and pulmonologists 1
• Early referral for lung transplantation evaluation is crucial for patients with advanced or rapidly progressive disease 1, 3
• Up to 85% of individuals with end-stage fibrotic ILD develop pulmonary hypertension, which may require specific treatment 3
• Antifibrotic therapy with nintedanib or pirfenidone slows annual FVC decline by approximately 44% to 57% in individuals with IPF and progressive pulmonary fibrosis 3