What is the recommended treatment for interstitial fibrosis?

Treatment of Interstitial Fibrosis

Antifibrotic therapy with pirfenidone or nintedanib is the recommended first-line treatment for interstitial fibrosis, particularly for idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF). 1

First-Line Treatment Options

Pirfenidone

• Recommended for patients with mild-to-moderate IPF (defined as FVC > 50% predicted and DLCO > 35% predicted) 1, 2
• Mechanism: Oral agent with anti-inflammatory, antioxidative, and antiproliferative effects 1
• Efficacy: Reduces the risk of disease progression by 30% (HR 0.70,95% CI 0.56-0.88) 1, 3
• Dosing: Gradual titration (267 mg three times daily in week 1,534 mg three times daily in week 2, and 801 mg three times daily thereafter) 4
• Monitoring: Liver function tests prior to initiation, monthly for first 6 months, then every 3 months 1, 2

Nintedanib

• Suggested for treatment of progressive pulmonary fibrosis (PPF) in patients who have failed standard management for fibrotic interstitial lung disease (ILD) 1
• Mechanism: Oral intracellular tyrosine kinase inhibitor that blocks pathways involved in fibrogenesis 1
• Efficacy: Slows annual FVC decline by approximately 107 ml compared to placebo in patients with PPF 1
• Benefits seen regardless of underlying ILD type or radiological pattern (UIP or non-UIP) 1

Treatment Algorithm Based on Disease Type

For Idiopathic Pulmonary Fibrosis (IPF):

1. Confirm diagnosis through clinical, radiographic, and if needed, histopathological evaluation 1
2. Assess disease severity using pulmonary function tests (FVC, DLCO) 1
3. For mild-to-moderate disease: Initiate pirfenidone or nintedanib 1, 3
4. Monitor disease progression with regular pulmonary function tests and clinical assessment 1, 2

For Progressive Pulmonary Fibrosis (non-IPF):

1. Consider nintedanib as first-line therapy after failure of standard management specific to the underlying ILD 1
2. Pirfenidone may be considered, though evidence is less robust than for nintedanib in non-IPF fibrotic ILDs 1, 4

Monitoring Treatment Response

• Regular assessment of FVC and DLCO (every 3-6 months) 1
• Quantitative CT assessment may provide objective measurement of disease progression 1
• Monitor for treatment-related adverse effects 1, 3

Managing Adverse Effects

Pirfenidone

• Common adverse effects: Nausea, rash, fatigue, diarrhea, photosensitivity, and elevated liver enzymes 1, 3
• Management strategies:
  • Gradual dose titration to improve tolerability 4
  • Take with food to reduce gastrointestinal effects 3
  • Avoid sun exposure and use sun protection for photosensitivity 1, 2
  • Smoking cessation (smoking increases pirfenidone metabolism) 1, 2

Nintedanib

• Common adverse effects: Diarrhea, nausea, abdominal pain, vomiting, elevated liver enzymes 1
• Management strategies:
  • Dose reduction may help manage side effects 1, 5
  • Temporary treatment interruption for severe adverse events 1

Treatment Considerations and Caveats

• Early treatment initiation is critical as both drugs slow progression but do not reverse existing fibrosis 5
• Consider switching antifibrotic agents if disease progression occurs or if adverse effects are intolerable 6
• Avoid combined therapy with corticosteroids and immunosuppressants (e.g., azathioprine) as this approach has shown increased mortality in IPF 1
• Oral anti-vitamin K anticoagulants are not recommended specifically for treating IPF 1
• Annual influenza and pneumococcal vaccinations are recommended for patients with IPF 1

Special Populations

• For patients with severe disease (FVC < 50% or DLCO < 35%), clinical trial data is limited, but treatment may still be considered on an individual basis 1, 3
• For patients who cannot tolerate first-line antifibrotic therapy, switching to an alternative antifibrotic may be effective and better tolerated 6

Future Directions

• Further research is needed on the efficacy of pirfenidone in specific types of non-IPF ILD manifesting PPF 1
• Quantitative CT assessment techniques are evolving and may provide more objective measures of disease progression in the future 1