What is the therapeutic management of fibrotic lung disease?

Therapeutic Management of Fibrotic Lung Disease

Antifibrotic medications (nintedanib and pirfenidone) are the cornerstone of treatment for idiopathic pulmonary fibrosis (IPF) and should be used as first-line therapy to slow disease progression and improve mortality outcomes. 1, 2

Treatment Approach for Idiopathic Pulmonary Fibrosis (IPF)

First-line Antifibrotic Therapy

• Nintedanib (intracellular inhibitor of tyrosine kinases) is recommended for patients with IPF to slow disease progression and reduce decline in forced vital capacity (FVC) 1
• Pirfenidone is recommended for patients with mild-to-moderate IPF (FVC ≥50% predicted and DLCO ≥35% predicted) to reduce FVC decline 1, 2
• Both medications have been shown to reduce the rate of lung function decline and risk of acute exacerbations 3

Medications to Avoid

• Strong recommendation AGAINST the combination therapy of N-acetylcysteine, azathioprine, and prednisone in IPF patients due to increased risk of harm 1
• Strong recommendation AGAINST glucocorticoids as first-line treatment for systemic sclerosis-associated ILD (SSc-ILD) due to risk of renal crisis 1
• Corticosteroids should be avoided or used cautiously in IPF as they have not shown efficacy in prospective trials 1

Supportive Care

• Long-term oxygen therapy is strongly recommended for patients with severe hypoxemia at rest 1
• Annual influenza vaccination and pneumococcal vaccination are recommended for all IPF patients 1
• Pulmonary rehabilitation programs should be initiated in patients with significant exercise limitation to improve walking distance, symptoms, and quality of life 1

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

First-line Therapy

• Mycophenolate is conditionally recommended as the preferred first-line therapy for most SARD-ILD 1
• Other first-line options (in order of preference) include rituximab, calcineurin inhibitors, and nintedanib, depending on the specific autoimmune disease 1

Progressive SARD-ILD Despite First-line Therapy

• For patients with progression despite first-line therapy, treatment options include:
  • Nintedanib (particularly with fibrotic disease or UIP pattern) 1
  • Rituximab 1
  • Tocilizumab 1
  • Cyclophosphamide (typically not used in combination with other therapies) 1
  • JAK inhibitors (particularly in patients with anti-MDA-5) 1

Rapidly Progressive ILD

• For rapidly progressive ILD associated with systemic autoimmune disease:
  • Intravenous glucocorticoids (except use with caution in systemic sclerosis) 1
  • Cyclophosphamide 1
  • Rituximab 1
  • Calcineurin inhibitors 1
  • Consider early lung transplant referral 1

Advanced Disease Management

Lung Transplantation

• Lung transplantation should be considered in all IPF patients <65 years of age with severe or worsening disease 1
• Early assessment at a lung transplantation center is advised 1
• Transplantation improves survival in patients with advanced IPF 1
• International guidelines recommend consideration for transplantation when DLCO <39% predicted and FVC has decreased by >10% over 6 months 1

Management of Acute Exacerbations

• Acute exacerbation is characterized by worsening dyspnoea (<30 days) with new opacities on imaging after ruling out other causes (infection, pulmonary embolism, heart failure) 1
• Treatment approaches for acute exacerbations may include high-dose corticosteroids, though evidence is limited 1

Emerging Therapies and Considerations

• Several novel antifibrotic agents are in clinical development targeting various pathways involved in fibrosis 4
• Antifibrotic therapy may be beneficial in non-IPF progressive fibrosing ILDs that share similar pathogenetic mechanisms 5, 3
• Management of side effects (particularly gastrointestinal) is crucial for treatment adherence with antifibrotic medications 6

Practical Considerations

• Liver function tests should be monitored with pirfenidone (prior to initiation, monthly for first 6 months, then every 3 months) 1
• Smoking cessation is essential and can affect pirfenidone metabolism 1
• Avoid concomitant use of pirfenidone with fluvoxamine or in patients with severe hepatic/renal impairment 1
• Common adverse effects of pirfenidone include nausea, rash, fatigue, diarrhea, and photosensitivity 1, 2
• Treatment decisions should consider the pace of disease progression, extent of fibrotic disease, and presence of UIP pattern on chest CT 1