When to start ESBRIET (pirfenidone) or Ofev (nintedanib) in IPF (Idiopathic Pulmonary Fibrosis) patients?

Initiation of Antifibrotic Therapy in Idiopathic Pulmonary Fibrosis

Pirfenidone (ESBRIET) or nintedanib (Ofev) should be initiated immediately upon diagnosis in patients with mild-to-moderate IPF, defined as FVC ≥50% predicted and DLCO ≥35% predicted, under the supervision of a physician experienced in IPF management. 1, 2

Patient Selection Criteria

Start Antifibrotic Therapy When:

• Immediately upon confirmed diagnosis of IPF with mild-to-moderate disease 1
• Before irreversible fibrosis has developed 1
• At first identification of clinical or physiological impairment 1
• At first documentation of decline in lung function 1

Disease Severity Assessment:

• Mild-to-moderate IPF: FVC ≥50% predicted and DLCO ≥35% predicted 1, 2
• Progressive pulmonary fibrosis (PPF) defined by at least two of the following within the past year 1:
  1. Worsening respiratory symptoms
  2. Physiological evidence of disease progression:
     • Absolute decline in FVC >5% predicted within 1 year
     • Absolute decline in DLCO >10% predicted within 1 year
  3. Radiological evidence of disease progression

Treatment Algorithm

1. Initial Assessment:

   • Confirm IPF diagnosis through clinical, radiological, and if necessary, histopathological criteria
   • Assess baseline pulmonary function (FVC, DLCO)
   • Evaluate for contraindications to therapy

2. Treatment Selection:

   • First-line options: Either pirfenidone or nintedanib
   • Both medications have shown efficacy in slowing disease progression 2, 3
   • Selection between agents based on:
     • Comorbidities
     • Potential drug interactions
     • Side effect profiles

3. Dosing and Titration:

   • Pirfenidone: Titrate over 14 days 2
     • Days 1-7: 267 mg three times daily (801 mg/day)
     • Days 8-14: 534 mg three times daily (1,602 mg/day)
     • Day 15 onward: 801 mg three times daily (2,403 mg/day)

4. Monitoring:

   • Pulmonary function tests every 3-6 months 1
   • Annual HRCT if clinical suspicion of worsening 1
   • For pirfenidone: Monthly liver function tests for first 6 months, then every 3 months 1, 2

Important Considerations

Efficacy:

• Both medications slow decline in FVC and disease progression 2, 3
• Pirfenidone may reduce IPF-related mortality (HR 0.48,95% CI 0.24–0.95) 2
• Real-world data shows functional stabilization even in older patients 4

Contraindications and Precautions:

• Pirfenidone:
  • Contraindicated with fluvoxamine use and severe hepatic/renal impairment 1, 2
  • Smoking must be discontinued (affects pirfenidone metabolism) 1
  • Avoid UV exposure due to photosensitivity risk 1, 2
  • Avoid concomitant omeprazole 1

Common Side Effects:

• Pirfenidone: Gastrointestinal symptoms, photosensitivity, rash, fatigue 2, 3
• Nintedanib: Primarily gastrointestinal effects (diarrhea, nausea, vomiting) 3, 5

Special Situations

Advanced Disease:

• Traditionally, antifibrotics were recommended for mild-to-moderate disease
• Emerging evidence suggests potential benefit in advanced disease 6
• Consider referral for lung transplantation at diagnosis if increased mortality risk 1

Comorbidities:

• Evaluate and treat existing comorbidities including:
  • Pulmonary hypertension
  • Gastroesophageal reflux
  • Obstructive sleep apnea
  • Lung cancer risk 1

Pitfalls to Avoid

1. Delaying treatment: Do not wait for disease progression before initiating therapy, as early treatment may preserve lung function 1

2. Inadequate monitoring: Regular follow-up is essential to assess treatment response and manage side effects

3. Discontinuing prematurely: Side effects can often be managed with dose adjustments rather than discontinuation 5

4. Missing comorbidities: Comprehensive assessment and management of comorbidities is essential for optimal outcomes

5. Neglecting supportive care: Consider oxygen therapy for hypoxemia and pulmonary rehabilitation for exercise limitation 1

Both antifibrotic medications have demonstrated efficacy in slowing disease progression, and treatment should be initiated promptly upon diagnosis to preserve lung function and improve outcomes.