What is the treatment protocol for interstitial lung disease (ILD)?

Treatment Protocol for Interstitial Lung Disease (ILD)

For patients with systemic autoimmune rheumatic disease (SARD)-associated ILD, mycophenolate is the preferred first-line treatment across all disease subtypes, with specific medication choices tailored based on disease type, severity, and progression. 1

First-Line Treatment Options by Disease Type

General First-Line Approach

• Mycophenolate is the preferred first-line agent for most SARD-ILD types due to its favorable efficacy and tolerability profile 1
• Rituximab is an alternative first-line option, particularly beneficial in rheumatoid arthritis-ILD with active inflammatory arthritis 1
• Glucocorticoids should be considered separately from other treatments:
  • Strongly recommended AGAINST use in systemic sclerosis-ILD due to risk of scleroderma renal crisis 1
  • Short-term glucocorticoids (≤3 months) may be considered for other SARD-ILD types 1

Disease-Specific Considerations

• Rheumatoid Arthritis-ILD:

  • Preferred: Mycophenolate, rituximab, tocilizumab 1
  • Avoid: Methotrexate, leflunomide, TNF inhibitors, abatacept 1

• Systemic Sclerosis-ILD:

  • Preferred: Mycophenolate, tocilizumab 1
  • Additional options: Cyclophosphamide 1
  • AVOID glucocorticoids (strong recommendation) 1

• Inflammatory Myopathies-ILD:

  • Preferred: Mycophenolate, rituximab 1
  • Additional options: Calcineurin inhibitors (especially for MDA-5 positive disease), JAK inhibitors 1

• Sjögren's Disease-ILD:

  • Preferred: Mycophenolate, rituximab 1
  • Additional options: Azathioprine, cyclophosphamide 1

Treatment for Progressive ILD Despite First-Line Therapy

When ILD progresses despite first-line treatment:

• Consider switching to an alternative agent or adding a second agent 1
• Avoid long-term glucocorticoids in all SARD-ILD types 1
• Treatment options include:
  • Nintedanib (particularly for fibrotic disease patterns) 1, 2
  • Rituximab (if not used as first-line) 1
  • Cyclophosphamide 1
  • Tocilizumab (especially for systemic sclerosis-ILD) 1, 2
  • JAK inhibitors (particularly for MDA-5 positive disease) 1
  • Consider autologous hematopoietic stem cell transplantation referral at experienced centers 1

Management of Rapidly Progressive ILD (RP-ILD)

RP-ILD requires aggressive intervention due to high mortality risk:

• Strongly recommended: Upfront combination therapy 1

  • Triple therapy for MDA-5 positive or suspected cases 1
  • Double or triple therapy for non-MDA-5 cases 1

• Treatment components:

  • IV glucocorticoids (except in systemic sclerosis where risk/benefit must be carefully weighed) 1
  • Plus 1-2 additional agents:
    • Rituximab or cyclophosphamide (preferred) 1
    • IVIG (especially when infection risk is high) 1
    • Calcineurin inhibitors (particularly tacrolimus for MDA-5 positive disease) 1
    • Mycophenolate 1
    • JAK inhibitors 1

• Early lung transplantation referral is conditionally recommended over delayed referral 1

• Plasma exchange should NOT be used as first-line therapy but may be considered for refractory cases 1

• Stem cell transplantation is conditionally NOT recommended as first-line treatment 1

Non-SARD ILD Treatment

• Idiopathic Pulmonary Fibrosis (IPF):

  • Antifibrotic therapy with nintedanib or pirfenidone slows FVC decline by 44-57% 2
  • Pirfenidone has demonstrated efficacy in reducing FVC decline compared to placebo in clinical trials 3

• Hypersensitivity Pneumonitis:

  • First step: Antigen identification and avoidance 4
  • If no improvement: Consider anti-inflammatory drugs like prednisolone 4

Supportive Care for All ILD Types

• Structured exercise therapy reduces symptoms and improves 6-minute walk test distance 2
• Supplemental oxygen for patients who desaturate below 88% on 6-minute walk test 2
• Consider lung transplantation for end-stage disease (median survival post-transplant: 5.2-6.7 years vs <2 years without transplant) 2
• For ILD-associated pulmonary hypertension: Consider inhaled treprostinil 2

Treatment Monitoring

• Multi-dimensional approach including:
  • Symptom tracking
  • Serial chest imaging
  • Pulmonary function tests (5% decline in FVC over 12 months indicates approximately 2-fold increase in mortality) 2, 4
  • 6-minute walking test 4

Important Caveats

• Co-management by rheumatologists and pulmonologists is strongly advised 1
• Shared decision-making is crucial given the conditional nature of most recommendations 1
• Treatment selection should account for disease severity, risk factors for progression, extrapulmonary manifestations, medication costs, and potential toxicities 1
• The hierarchy of treatment options should not be used by insurers to mandate a specific prescribing order 1