What are the management options for interstitial lung disease?

Management of Interstitial Lung Disease

Mycophenolate mofetil is the preferred first-line treatment for most types of interstitial lung disease (ILD), particularly those associated with systemic autoimmune rheumatic diseases (SARD-ILD). 1, 2

First-Line Treatment Options by ILD Type

Systemic Autoimmune Rheumatic Disease-ILD (SARD-ILD)

• Preferred first-line agent:
  • Mycophenolate mofetil 1, 2
• Additional first-line options:
  • Rituximab
  • Azathioprine
  • Cyclophosphamide 1

Specific SARD-ILD Subtypes

1. Systemic Sclerosis-ILD (SSc-ILD):

   • Strongly recommended against: Long-term glucocorticoids (risk of scleroderma renal crisis) 1
   • Recommended options: Mycophenolate, nintedanib 1, 3

2. Rheumatoid Arthritis-ILD (RA-ILD):

   • Treatment options: Mycophenolate, rituximab, tocilizumab 1
   • For progressive disease: Consider adding pirfenidone 1, 2

3. Idiopathic Inflammatory Myopathy-ILD (IIM-ILD):

   • Additional options: Calcineurin inhibitors (preferably tacrolimus), JAK inhibitors 1
   • For anti-MDA-5 associated disease: Consider JAK inhibitors 1

Management of Progressive ILD

For patients with progression despite first-line treatment:

1. All SARD-ILD types:

   • Mycophenolate, rituximab, cyclophosphamide, and nintedanib are conditionally recommended 1
   • Strongly recommended against long-term glucocorticoids in SSc-ILD 1
   • Conditionally recommended against long-term glucocorticoids in other SARD-ILD 1

2. Disease-specific options for progressive ILD:

   • RA-ILD: Add pirfenidone, consider tocilizumab 1, 2
   • SSc-ILD: Consider tocilizumab, nintedanib, referral for stem cell or lung transplantation 1
   • IIM-ILD: Consider calcineurin inhibitors, JAK inhibitors, IVIG 1

Management of Rapidly Progressive ILD (RP-ILD)

For patients with rapidly progressive disease:

• First-line treatment: Pulse intravenous methylprednisolone 1
• Additional options: Rituximab, cyclophosphamide, IVIG, mycophenolate, calcineurin inhibitors, JAK inhibitors 1
• Combination therapy: Upfront combination therapy is conditionally recommended over monotherapy 1
• Early referral: Consider early referral for lung transplantation 1

Antifibrotic Therapy

• Nintedanib: Conditionally recommended for SSc-ILD and progressive fibrosing ILD 1, 2, 3
• Pirfenidone:
  • Conditionally recommended for progressive RA-ILD 1, 2
  • Slows annual FVC decline by approximately 44-57% in IPF 4, 5
  • Not recommended for other SARD-ILD types 1

Monitoring and Assessment

• Pulmonary function tests (PFTs): Regular monitoring is essential; a 5% decline in FVC over 12 months is associated with approximately 2-fold increase in mortality 2, 5
• High-resolution CT scans: Recommended for baseline assessment and as needed to evaluate progression 1, 2
• Symptom assessment: Regular evaluation of dyspnea, cough, and exercise tolerance 2

Common Pitfalls and Caveats

1. Delayed treatment: Early intervention is crucial as delay can lead to irreversible progressive fibrosis 2
2. Inadequate monitoring: Regular PFTs and symptom assessment are essential for detecting progression 2, 5
3. Glucocorticoid use in SSc-ILD: Strongly avoid long-term glucocorticoids due to risk of scleroderma renal crisis; if absolutely necessary, use lowest effective dose (<15 mg/day) 1
4. Neglecting comorbidities: GERD and pulmonary hypertension can exacerbate ILD and should be managed appropriately 2
5. Failure to recognize rapidly progressive disease: Requires prompt, aggressive intervention with combination therapy 1

Special Considerations

• Pulmonary hypertension: Up to 85% of individuals with end-stage fibrotic ILD develop pulmonary hypertension; consider inhaled treprostinil which can improve walking distance and respiratory symptoms 5
• Exercise therapy: Structured exercise therapy reduces symptoms and improves 6-minute walk test distance 5
• Oxygen therapy: Reduces symptoms and improves quality of life in patients who desaturate below 88% on a 6-minute walk test 5
• Multidisciplinary approach: Collaboration between pulmonologists and rheumatologists is essential for optimal management of CTD-ILD 1

For patients with advanced disease not responding to medical therapy, lung transplantation should be considered, as it can improve survival from less than 2 years to a median of 5.2-6.7 years 5.