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

Treatment of Interstitial Lung Disease (ILD)

Mycophenolate mofetil is the preferred first-line treatment for most types of interstitial lung disease, with specific treatment modifications based on the underlying cause and disease progression. 1

First-Line Treatment Options Based on ILD Subtype

For Non-SSc SARD-ILD (Systemic Autoimmune Rheumatic Disease-ILD):

• First-line therapy:
  • Mycophenolate mofetil (1000-1500 mg twice daily) 2, 1
  • Short-term glucocorticoids as adjunctive therapy (initial dose 0.5-1 mg/kg/day, maximum 60 mg/day, with taper to ≤10 mg over 3 months) 2
  • Alternative options: azathioprine, rituximab, or cyclophosphamide 2

For SSc-ILD (Systemic Sclerosis-ILD):

• First-line therapy:
  • Mycophenolate mofetil 2
  • Tocilizumab (for SSc-ILD and MCTD-ILD) 2
  • Nintedanib (especially with progressive fibrosing phenotype) 2
  • AVOID glucocorticoids (strongly recommended against due to risk of renal crisis) 2

For IIM-ILD (Idiopathic Inflammatory Myopathy-ILD):

• First-line therapy:
  • Mycophenolate mofetil 2
  • JAK inhibitors 2
  • Calcineurin inhibitors (tacrolimus preferred over cyclosporine) 2
  • Short-term glucocorticoids 2

For RA-ILD (Rheumatoid Arthritis-ILD):

• First-line therapy:
  • Mycophenolate mofetil 2
  • No consensus on nintedanib as first-line therapy 2
  • Pirfenidone is recommended as a second-line option for progressive disease 2

Treatment for Progressive Disease

Progressive disease is defined as:

• Decline in FVC ≥10% predicted, or
• Decline in FVC 5-10% predicted with worsening respiratory symptoms or increased fibrosis on HRCT, or
• Worsening respiratory symptoms with increased fibrosis on HRCT 2

For patients with progressive disease despite first-line therapy:

1. For all SARD-ILD with progression:

   • Mycophenolate (if not already used)
   • Rituximab
   • Cyclophosphamide
   • Nintedanib 2

2. For RA-ILD with progression:

   • Add pirfenidone 2
   • Consider tocilizumab 2

3. For SSc-ILD with progression:

   • Consider tocilizumab 2
   • Consider referral for stem cell transplantation or lung transplantation 2

4. For IIM-ILD with progression:

   • Consider calcineurin inhibitors 2
   • Consider JAK inhibitors 2
   • Consider IVIG 2

Monitoring and Disease Assessment

Regular monitoring is essential to detect progression and adjust treatment:

• Pulmonary Function Tests (PFTs):

  • Every 3-6 months for the first 1-2 years 2
  • More frequent (every 3 months) for moderate-to-severe ILD or progressive disease 2
  • A 5% decline in FVC over 12 months is associated with approximately 2-fold increase in mortality 3

• High-Resolution CT (HRCT):

  • At baseline
  • Repeat within 3-6 months to 1 year depending on disease, pattern, and extent 2
  • Additional scans as clinically indicated 1

Important Clinical Considerations and Pitfalls

1. Avoid long-term high-dose glucocorticoids due to significant adverse effects, especially in SSc-ILD 2, 1

2. Recognize rapidly progressive disease which requires aggressive combination therapy and early consideration for lung transplantation 1

3. Address comorbidities such as GERD and pulmonary hypertension, which may exacerbate ILD 1

4. Don't delay treatment escalation as this can lead to irreversible fibrosis 1

5. Consider antifibrotic therapy for progressive fibrosing phenotypes regardless of underlying etiology 4, 5

6. Multidisciplinary evaluation is essential for accurate diagnosis and treatment planning, involving pulmonologists and rheumatologists 2

7. Early referral for lung transplantation should be considered for patients with advanced ILD 1

8. Exercise and pulmonary rehabilitation can improve symptoms and 6-minute walk test distance 3

9. Oxygen therapy is recommended for patients who desaturate below 88% on a 6-minute walk test 3

By following these evidence-based guidelines and carefully monitoring disease progression, the morbidity and mortality associated with ILD can be reduced and quality of life improved for patients with this challenging group of disorders.