What are the treatment options for interstitial lung disease (ILD)?

Treatment Options for Interstitial Lung Disease (ILD)

Mycophenolate is the preferred first-line treatment for most types of interstitial lung disease associated with systemic autoimmune rheumatic diseases (SARD-ILD), with treatment selection guided by the underlying disease and individual patient factors. 1

First-Line Treatment Options by ILD Type

Systemic Autoimmune Rheumatic Disease-Associated ILD (SARD-ILD)

Preferred First-Line Options:

• Mycophenolate - Conditionally recommended as first-line therapy across all SARD-ILD subtypes 1
• Azathioprine - Conditionally recommended as an alternative first-line option 1
• Rituximab - Conditionally recommended, particularly beneficial in rheumatoid arthritis-associated ILD (RA-ILD) with active inflammatory arthritis 1
• Cyclophosphamide - Conditionally recommended, especially for more severe or rapidly progressive cases 1

Disease-Specific First-Line Options:

• Systemic Sclerosis-ILD (SSc-ILD):

  • Tocilizumab - Conditionally recommended 1
  • Nintedanib - Conditionally recommended 1
  • Strong recommendation against glucocorticoids due to risk of scleroderma renal crisis 1

• Inflammatory Myopathy-ILD (IIM-ILD):

  • JAK inhibitors - Conditionally recommended 1
  • Calcineurin inhibitors (tacrolimus, cyclosporine) - Conditionally recommended 1
  • Short-term glucocorticoids - Conditionally recommended 1

• Rheumatoid Arthritis-ILD (RA-ILD):

  • Short-term glucocorticoids - Conditionally recommended 1
  • Panel was unable to reach consensus on nintedanib as first-line therapy 1

• Mixed Connective Tissue Disease-ILD (MCTD-ILD):

  • Tocilizumab - Conditionally recommended 1
  • Short-term glucocorticoids - Conditionally recommended (use cautiously in patients with SSc phenotype) 1

• Sjögren's Disease-ILD (SjD-ILD):

  • Short-term glucocorticoids - Conditionally recommended 1

Treatments Not Recommended as First-Line for SARD-ILD:

• Methotrexate 1
• Leflunomide 1
• TNF inhibitors 1
• Abatacept 1
• Pirfenidone (for all SARD-ILD types) 1
• IVIG or plasma exchange 1

Treatment for Progressive ILD Despite First-Line Therapy

For Progressive SARD-ILD:

• Mycophenolate - If not used as first-line 1
• Rituximab - Conditionally recommended 1
• Cyclophosphamide - Conditionally recommended 1
• Nintedanib - Conditionally recommended 1
• Against long-term glucocorticoids - Strong recommendation against for SSc-ILD, conditional for other types 1

Disease-Specific Options for Progressive ILD:

• RA-ILD:

  • Pirfenidone - Conditionally recommended 1
  • Tocilizumab - Conditionally recommended 1

• SSc-ILD and MCTD-ILD:

  • Tocilizumab - Conditionally recommended 1
  • For SSc-ILD: Consider referral for stem cell or lung transplantation 1

• IIM-ILD:

  • Calcineurin inhibitors - Conditionally recommended 1
  • JAK inhibitors - Conditionally recommended 1
  • IVIG - Conditionally recommended 1

• MCTD-ILD:

  • IVIG - Conditionally recommended 1

Treatment for Rapidly Progressive ILD (RP-ILD)

First-Line Options for RP-ILD:

• Pulse intravenous methylprednisolone - Conditionally recommended 1
• Upfront combination therapy - Conditionally recommended over monotherapy 1
  • Triple therapy (glucocorticoids plus two agents) for confirmed or suspected MDA-5-associated disease 1
  • Double or triple therapy for other RP-ILD 1

Recommended Agents for RP-ILD:

• Rituximab 1
• Cyclophosphamide 1
• IVIG 1
• Mycophenolate 1
• Calcineurin inhibitors 1
• JAK inhibitors 1

Not Recommended for RP-ILD:

• Methotrexate, leflunomide, azathioprine 1
• TNF inhibitors, abatacept, tocilizumab 1
• Nintedanib, pirfenidone 1
• Plasma exchange 1
• Stem cell transplantation as first-line 1

Lung Transplantation:

• Early referral for lung transplantation is conditionally recommended for RP-ILD 1

Antifibrotic Therapy

Nintedanib:

• Conditionally recommended for SSc-ILD as first-line 1
• Conditionally recommended for progressive SARD-ILD 1
• Slows annual FVC decline by approximately 44% to 57% in IPF, SSc-ILD, and progressive pulmonary fibrosis 2

Pirfenidone:

• Conditionally recommended against as first-line for SARD-ILD 1
• Conditionally recommended for progressive RA-ILD 1
• Reduces decline in FVC in IPF patients (mean treatment difference 193 mL at Week 52) 3

Non-Pharmacological Management

• Structured exercise therapy - Reduces symptoms and improves 6-minute walk test distance 2
• Oxygen therapy - Improves symptoms and quality of life in patients who desaturate below 88% on 6-minute walk test 2
• Multidisciplinary approach - Co-management by rheumatologists and pulmonologists is strongly advised for optimal diagnosis and treatment 1, 4

Important Clinical Considerations

• Treatment selection should be guided by ILD severity, risk factors for progression, extrapulmonary manifestations, cost, and potential toxicity 1
• Early identification of progressive pulmonary fibrosis is crucial for timely initiation of antifibrotic therapy 1
• Regular monitoring with pulmonary function tests and HRCT is essential to assess treatment response and disease progression 1
• For patients with end-stage fibrotic ILD who develop pulmonary hypertension (up to 85%), inhaled treprostinil may improve walking distance and respiratory symptoms 2
• Lung transplantation should be considered for advanced ILD, with median survival of 5.2-6.7 years post-transplant compared to <2 years without transplant 2