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

Treatment for Interstitial Lung Disease (ILD)

The treatment of interstitial lung disease should be tailored to the specific ILD subtype, with mycophenolate mofetil being the preferred first-line agent for most connective tissue disease-associated ILDs, while antifibrotic medications like nintedanib are recommended for systemic sclerosis-ILD and progressive fibrosing ILDs. 1, 2

First-Line Treatment Based on ILD Subtype

Connective Tissue Disease-Associated ILD (CTD-ILD)

• For all CTD-ILD except systemic sclerosis (SSc-ILD):

  • Glucocorticoids (prednisone) as first-line treatment 1
  • Typically combined with immunosuppressive agents 1
  • Oral prednisone for most cases; IV pulse methylprednisolone for acute/severe ILD 1

• For SSc-ILD:

  • STRONGLY AVOID glucocorticoids as first-line treatment 1
  • Mycophenolate mofetil is preferred first-line agent 2
  • Nintedanib is conditionally recommended as first-line option 1
  • Tocilizumab is a conditionally recommended alternative 1, 2

• For inflammatory myopathy-associated ILD (IIM-ILD):

  • Mycophenolate mofetil as preferred first-line agent 2
  • JAK inhibitors conditionally recommended 1
  • Calcineurin inhibitors (cyclosporine, tacrolimus) conditionally recommended 1, 2

• For rheumatoid arthritis-associated ILD (RA-ILD):

  • Mycophenolate mofetil as preferred first-line agent 2
  • No consensus on nintedanib as first-line option 1

Idiopathic Pulmonary Fibrosis (IPF)

• Antifibrotic therapy with nintedanib or pirfenidone 3
  • Slows annual FVC decline by approximately 44% to 57% 3
  • Nintedanib demonstrated efficacy in clinical trials with statistically significant reduction in FVC decline 4
  • Pirfenidone showed reduction in mean FVC decline in clinical trials 5

Treatment for Progressive Disease Despite First-Line Therapy

• For all SARD-ILD with progression:

  • Mycophenolate, rituximab, cyclophosphamide, and nintedanib are conditionally recommended 1
  • Avoid long-term glucocorticoids (strongly recommended against in SSc-ILD) 1

• For specific subtypes with progression:

  • RA-ILD: Consider adding pirfenidone 1
  • SSc-ILD, MCTD-ILD, RA-ILD: Consider tocilizumab 1
  • IIM-ILD: Consider calcineurin inhibitors or JAK inhibitors 1, 2
  • Refractory IIM-ILD: Consider IVIG as add-on therapy, especially with respiratory muscle weakness 2

Monitoring Disease Progression

• Regular pulmonary function tests (PFTs):

  • Every 3-6 months for moderate-to-severe ILD
  • Every 6 months for 1-2 years for mild ILD (FVC ≥70% and <20% fibrosis on HRCT) 2
  • A 5% decline in FVC over 12 months is associated with doubled mortality 2, 3

• HRCT follow-up:

  • Initial HRCT within 6 months to determine progression rate 2
  • Progression defined as: decline in FVC ≥10% predicted, decline in FVC 5-10% with worsening symptoms or increased fibrosis on HRCT, or worsening symptoms with increased fibrosis 1

Supportive Care and Additional Considerations

• Oxygen therapy: For patients who desaturate below 88% on 6-minute walk test 3

• Pulmonary rehabilitation: Structured exercise therapy reduces symptoms and improves 6-minute walk distance 3

• Preventive care:

  • Pneumocystis jirovecii pneumonia prophylaxis for patients on high-dose corticosteroids 2
  • Calcium and vitamin D supplementation 2
  • Vaccinations (influenza, pneumococcus, COVID-19) 2

• Advanced disease management:

  • Early referral for lung transplantation for progressive disease 2
  • Consider treatment for pulmonary hypertension if present 3

Pitfalls and Caveats

• Avoid glucocorticoids in SSc-ILD: Strong recommendation against their use due to poor outcomes 1

• Avoid combination therapy without evidence of benefit: For patients with SARD-ILD receiving mycophenolate without evidence of progression, adding nintedanib or pirfenidone is not recommended 1

• Monitor for medication side effects: Particularly with long-term corticosteroid use 2

• Recognize progressive fibrosing phenotype: Some ILDs may develop a progressive fibrosing phenotype requiring more aggressive therapy 6

• Consider underlying cause: Always address potential underlying causes such as environmental exposures in hypersensitivity pneumonitis 6