What is the treatment for fibrotic Non-Specific Interstitial Pneumonia (NSIP)?

Treatment of Fibrotic Non-Specific Interstitial Pneumonia (NSIP)

For fibrotic NSIP, nintedanib is recommended as first-line treatment for patients who have failed standard management, with immunosuppressive therapy as the foundation of initial treatment. 1

Initial Assessment and Classification

• Determine if the NSIP is idiopathic or secondary to other conditions:

  • Complete autoimmune serologies to rule out connective tissue disease
  • Thorough exposure history to exclude hypersensitivity pneumonitis
  • High-resolution CT scan to confirm NSIP pattern
  • Consider lung biopsy if diagnosis is uncertain

• Identify the NSIP phenotype, which guides treatment approach 2:

  1. Inflammatory type: Prominent lymphocytic inflammation on biopsy/BAL, mixed NSIP/organizing pneumonia pattern on HRCT
  2. Highly fibrotic type: Prominent reticular changes and traction bronchiectasis on HRCT, high fibrotic background on biopsy

Treatment Algorithm

First-line Treatment for Inflammatory NSIP

1. Corticosteroids:

   • Initial high-dose prednisone (40-100 mg daily) for 2-4 months 1
   • Gradual taper based on clinical response
   • Monitor for improvement within 3-6 months

2. Immunosuppressive agents (often used in combination with corticosteroids):

   • Mycophenolate mofetil (MMF): 2g daily 3
   • Alternative: Azathioprine or cyclophosphamide

Treatment for Fibrotic NSIP

1. Antifibrotic therapy:

   • Nintedanib: 150mg twice daily 1

     • Shown to reduce FVC decline in progressive pulmonary fibrosis
     • Monitor for gastrointestinal side effects and liver function abnormalities

   • Pirfenidone: Consider as alternative antifibrotic 1

     • Though evidence is limited specifically for NSIP
     • The ATS/ERS/JRS/ALAT guideline recommends further research into pirfenidone for fibrotic NSIP

2. Combination therapy for refractory cases:

   • Consider rituximab plus MMF combination for progressive disease 3
   • Recent evidence shows this combination was superior to MMF alone in patients with NSIP pattern, with a between-group difference in FVC of 3.60% (95% CI 0.41-6.80; p=0.0273)

Monitoring and Follow-up

• Pulmonary function tests every 3-6 months 4
• HRCT annually or if unexplained clinical deterioration 4
• Regular assessment of oxygen saturation
• Monitor for treatment-related adverse effects

Supportive Care

• Oxygen therapy for patients with resting or exertional hypoxemia 4
• Pulmonary rehabilitation to improve exercise capacity and quality of life 4
• Vaccination against influenza and pneumococcal disease 4
• Cough management with targeted therapies 4

Advanced Disease Management

• Consider lung transplantation evaluation for patients under 65 years with severe or progressive disease 4
• Early integration of palliative care for symptom management 4

Important Considerations

• Fibrotic NSIP has better prognosis than IPF, with 5-year mortality around 15-20% 1
• The inflammatory subtype typically responds better to immunosuppressive therapy than the fibrotic subtype 2
• Highly fibrotic NSIP has marginal risk of evolving into "full-blown IPF" and may be less responsive to immunosuppression 2
• Combination of antifibrotic and immunosuppressive therapy is an emerging approach that requires further study

Treatment Pitfalls to Avoid

1. Failing to distinguish between inflammatory and fibrotic NSIP phenotypes
2. Overreliance on corticosteroids alone for fibrotic NSIP
3. Inadequate monitoring for disease progression
4. Delayed referral for lung transplantation evaluation in progressive cases
5. Not addressing comorbidities that may worsen outcomes

The management of fibrotic NSIP requires careful phenotyping and a strategic approach that combines immunosuppressive and antifibrotic therapies based on disease characteristics and progression.