What is the recommended management for a patient with progressive pulmonary fibrosis?

Management of Progressive Pulmonary Fibrosis

Nintedanib is the recommended first-line treatment for patients with progressive pulmonary fibrosis (PPF) who have failed standard management for fibrotic interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF). 1

Definition and Diagnosis of Progressive Pulmonary Fibrosis

Progressive pulmonary fibrosis is defined as the presence of at least two of the following three criteria within the previous year in patients with interstitial lung disease with radiological pulmonary fibrosis (other than IPF) 1, 2:

1. Worsening respiratory symptoms
2. Physiological progression (particularly FVC decline >5% or DLCO decline >10%)
3. Radiological progression (increased reticular abnormality, traction bronchiectasis, or honeycombing)

Treatment Algorithm for Progressive Pulmonary Fibrosis

First-Line Treatment

• Nintedanib (150 mg twice daily) is recommended as first-line therapy for PPF in patients who have failed standard management for fibrotic ILD 1, 3
  • Mechanism: Tyrosine kinase inhibitor that blocks pathways involved in fibrogenesis
  • Evidence: INBUILD trial showed significantly less mean annual FVC decline (107 ml) in the nintedanib arm compared to placebo 1
  • Efficacy: Slows disease progression in both IPF and non-IPF progressive pulmonary fibrosis 3, 4

Alternative Treatment Option

• Pirfenidone (801 mg three times daily) may be considered, though evidence is less robust 1, 3
  • The ATS/ERS/JRS/ALAT guideline committee made no formal recommendation for pirfenidone in PPF due to insufficient evidence, with 38% of committee members abstaining from voting 1
  • Meta-analyses show pirfenidone may provide benefits in slowing FVC decline (mean difference 100.0 ml) and protecting DLCO 5

Common Side Effects to Monitor

• Nintedanib: Diarrhea (2.8x increased risk), nausea (3.1x), vomiting (3.6x), abdominal pain (4.2x), elevated liver enzymes (3.2-3.6x), weight loss (3.7x) 1
• Pirfenidone: Nausea, rash, fatigue, photosensitivity, gastrointestinal discomfort 3, 6, 7

Monitoring and Supportive Care

1. Regular Monitoring:

   • Pulmonary function tests every 3-6 months (FVC and DLCO) 3
   • HRCT within first 3 years after diagnosis 3
   • Clinical assessment for worsening respiratory symptoms 3

2. Management of Comorbidities:

   • Evaluate and treat pulmonary hypertension, gastroesophageal reflux, obstructive sleep apnea, and other comorbidities 3
   • Screen for obstructive sleep apnea if clinical signs are present 3

3. Supportive Measures:

   • Oxygen therapy for hypoxemia (PaO₂ < 55 mmHg or SpO₂ < 88%) 3
   • Pulmonary rehabilitation to improve exercise capacity and quality of life 3
   • Annual influenza and pneumococcal vaccinations 3
   • Smoking cessation for current smokers 3

4. Consider Lung Transplantation:

   • Early referral for patients under 65 years with severe or worsening disease 3
   • Particularly for those with DLCO <39% predicted or FVC decrease >10% over 6 months 3

Important Clinical Considerations

• The quality of evidence for nintedanib in PPF is rated as low, but still supports its use given the significant reduction in FVC decline 1
• The quality of evidence for pirfenidone in PPF is rated as very low, with existing randomized trials encompassing only 380 patients 1, 5
• Antifibrotic therapy shows similar efficacy in slowing FVC decline whether the underlying condition is IPF or non-IPF with progressive fibrosis 4
• Treatment discontinuation due to adverse events may be higher with nintedanib (70.6%) compared to pirfenidone (31.2%) 6, highlighting the importance of managing side effects

Pitfalls to Avoid

• Failing to recognize PPF early - monitor for subtle changes in symptoms, lung function, and imaging
• Not managing medication side effects aggressively, which can lead to treatment discontinuation
• Overlooking the importance of supportive care measures alongside antifibrotic therapy
• Delaying referral for lung transplantation evaluation in appropriate candidates
• Not informing patients about available clinical trials, which is a common pitfall in management 3