What is the first-line treatment for pulmonary fibrosis, specifically idiopathic pulmonary fibrosis (IPF)?

First-Line Treatment for Idiopathic Pulmonary Fibrosis (IPF)

Nintedanib and pirfenidone are the only approved antifibrotic medications for the first-line treatment of idiopathic pulmonary fibrosis (IPF), as they have been shown to reduce the decline in pulmonary function and improve clinical outcomes. 1

Antifibrotic Therapy Options

Pirfenidone

• Dosing: 2,403 mg/day (administered as three doses daily with food) 2
• Mechanism: Antiinflammatory, antioxidative, and antiproliferative effects 3
• Evidence of efficacy:
  • Reduces decline in forced vital capacity (FVC) compared to placebo (mean treatment difference 193 mL at 52 weeks) 2
  • Reduces risk of disease progression by 30% (HR 0.70,95% CI 0.56–0.88) 3
  • FDA-approved specifically for IPF treatment 2
• Monitoring: Regular liver function tests and clinical assessment 1

Nintedanib

• Dosing: 150 mg twice daily 1
• Monitoring: Regular assessment of FVC decline 1

Patient Selection Considerations

• Eligible patients typically have:
  • Confirmed diagnosis of IPF with exclusion of other causes of interstitial lung disease
  • %FVC ≥50% at baseline
  • %DLCO ≥30-35% at baseline 2
• Both medications are indicated for mild-to-moderate IPF 3, 4

Monitoring Disease Progression

• Pulmonary function tests every 3-6 months 1
• HRCT annually or if there is suspicion of worsening 1
• Regular assessment of symptoms and oxygen saturation 1

Important Considerations

• Early treatment is critical: IPF is a progressive, irreversible, and fatal disease with average life expectancy of only 3-4 years if untreated 5
• Disease progression is linear: Even patients with well-preserved lung function at baseline experience similar rates of decline as those with more advanced disease 5
• Side effect management: Most patients can tolerate antifibrotic therapy with appropriate dose adjustments to manage side effects without compromising efficacy 5
• Common side effects of pirfenidone: Nausea, anorexia, and photosensitivity dermatitis 6

What NOT to Use

• Corticosteroids: Should not be used routinely in IPF as they have not been shown to improve survival and are associated with substantial morbidity 1
• Triple therapy (prednisone, azathioprine, and N-acetylcysteine): Harmful and should not be used 3

Supportive Care

• Pulmonary rehabilitation to improve exercise capacity and quality of life 1
• Oxygen therapy for patients with clinically significant resting hypoxemia or exercise desaturation 1
• Annual influenza and pneumococcal vaccinations 1
• Early integration of palliative care for symptom management 1
• Lung transplantation consideration for eligible patients under 65 years with severe or worsening disease 1

Caveats

• Despite proven benefits, many IPF patients remain untreated due to physician perception that the disease is stable or concerns about side effects 5
• Individual clinical trials have not been powered to show reductions in mortality, but pooled analyses and observational studies suggest antifibrotic therapies improve life expectancy 5
• The pharmacotherapeutic landscape for IPF continues to evolve with numerous new drugs in clinical development 7