What is the initial treatment approach for interstitial lung disease?

Initial Treatment Approach for Interstitial Lung Disease

For patients with interstitial lung disease (ILD), mycophenolate mofetil is the preferred first-line treatment option across all systemic autoimmune rheumatic disease (SARD) subtypes, with treatment selection tailored to the specific ILD subtype and underlying disease. 1

Treatment Algorithm Based on ILD Subtype

Connective Tissue Disease-Associated ILD (CTD-ILD)

First-Line Options (in order of preference):

1. Mycophenolate mofetil (preferred first-line across all SARD-ILD subtypes)
2. Rituximab (particularly beneficial for rheumatoid arthritis-ILD with active inflammatory arthritis)
3. Nintedanib (for progressive fibrosing phenotypes)
4. Tocilizumab (for systemic sclerosis and rheumatoid arthritis)
5. Cyclophosphamide (for severe, rapidly progressive disease)

Glucocorticoid Considerations:

• Strongly avoid in systemic sclerosis-ILD due to risk of scleroderma renal crisis 1
• Short-term use only in other CTD-ILD subtypes
• Pulse IV methylprednisolone may be considered for rapidly progressive ILD 2

Idiopathic Pulmonary Fibrosis (IPF)

First-Line Options:

• Antifibrotic therapy:
  • Nintedanib or Pirfenidone (slows FVC decline by 44-57%) 3, 4
• Avoid corticosteroids in IPF as they may increase mortality 1

Rapidly Progressive ILD (RP-ILD)

First-Line Approach:

• Combination therapy is recommended over monotherapy 1
• Triple therapy for MDA-5 associated RP-ILD:
  • IV glucocorticoids
  • Plus 2 additional agents (rituximab, cyclophosphamide, IVIG, tacrolimus, or mycophenolate) 1
• Early referral for lung transplantation is conditionally recommended 1

Treatment Selection Based on Disease Severity

Mild to Moderate Disease:

• Mycophenolate mofetil (2-3 g/day)
• Monitor every 3-6 months with pulmonary function tests 5

Severe or Progressive Disease:

• Rituximab or Cyclophosphamide (preferred over other options)
• Consider nintedanib for progressive fibrosing phenotypes
• Consider calcineurin inhibitors (tacrolimus) particularly for inflammatory myopathy-associated ILD 1, 2

Refractory Disease:

• JAK inhibitors for refractory IIM-ILD (particularly with anti-MDA-5) 5
• IVIG as add-on therapy, especially when infection is a concern 1
• Combination therapy with multiple agents 1

Monitoring and Follow-up

• Pulmonary function tests every 3-6 months
• HRCT when clinically indicated
• Monitor for disease progression: A 5% decline in FVC over 12 months is associated with doubled mortality 5, 4
• Assess for treatment complications: Monitor CBC, LFTs, renal function based on specific medication 1

Important Caveats and Pitfalls

1. Avoid methotrexate, leflunomide, and TNF inhibitors for ILD treatment as they may worsen lung disease 1

2. Calcineurin inhibitors (tacrolimus/cyclosporine) require close monitoring for renal toxicity and hypertension 1

3. Early referral for lung transplantation should be considered for progressive disease despite optimal medical management 1

4. Supportive care including oxygen therapy and pulmonary rehabilitation improves symptoms and quality of life 5, 4

5. Investigate persistent cough in ILD patients for other causes including GERD, asthma, or upper airway cough syndrome 1

The treatment approach to ILD requires careful consideration of the underlying disease, pattern of lung involvement, and disease severity. While mycophenolate is generally preferred as first-line therapy for CTD-ILD, antifibrotic agents are the mainstay for IPF, and combination therapy is essential for rapidly progressive disease. Early intervention is critical as ILD can progress rapidly and lead to significant morbidity and mortality.