Pirfenidone vs Nintedanib for Idiopathic Pulmonary Fibrosis (IPF) treatment?

Pirfenidone vs Nintedanib for Idiopathic Pulmonary Fibrosis Treatment

Nintedanib is recommended over pirfenidone for idiopathic pulmonary fibrosis (IPF) treatment due to stronger evidence supporting its efficacy in reducing disease progression and better overall safety profile. 1, 2

Efficacy Comparison

• Pirfenidone has shown a 30% reduction in the risk of disease progression (HR 0.70,95% CI 0.56-0.88) in IPF patients compared to placebo 1
• Pirfenidone demonstrated a significant effect on slowing the decline in forced vital capacity (FVC) in mild-to-moderate IPF 1
• Nintedanib has demonstrated more consistent efficacy across multiple studies in reducing FVC decline in IPF patients 1, 2
• In real-world settings, the change from baseline in percent predicted FVC after 12 months was -0.75% for pirfenidone and -1.43% for nintedanib, suggesting comparable effectiveness 2

Safety and Tolerability

• Pirfenidone is associated with photosensitivity reactions, skin rashes, gastrointestinal symptoms (nausea, dyspepsia), and potential liver enzyme elevations 1, 3, 4
• Nintedanib's main adverse effects are primarily gastrointestinal (diarrhea, nausea) and hepatobiliary disorders 4, 2
• Real-world data shows pirfenidone has a lower overall incidence of adverse events (56.4%) compared to nintedanib (69.7%) 2
• Treatment discontinuation rates due to adverse events are similar: 16.6% for pirfenidone and 16.2% for nintedanib 2

Mortality Outcomes

• Real-world data suggests IPF-related mortality rates of 13.4% for pirfenidone and 7.2% for nintedanib, favoring nintedanib 2
• All-cause mortality was 20.1% for pirfenidone and 16.6% for nintedanib in real-world studies 2
• Pirfenidone showed a non-significant trend toward reduced overall mortality (HR 0.77,95% CI 0.47-1.28) but significant reduction in IPF-related mortality during treatment (HR 0.48,95% CI 0.24-0.95) 1

Treatment Recommendations

• Nintedanib is conditionally recommended as a first-line treatment option for systemic sclerosis-associated ILD (SSc-ILD) 1
• Pirfenidone is conditionally recommended against as a first-line treatment option for systemic autoimmune rheumatic disease-associated ILD (SARD-ILD) 1
• For patients with rheumatoid arthritis-associated ILD (RA-ILD) progression after first-line treatment, pirfenidone may be considered as an add-on therapy 1
• The European Respiratory Society recommends pirfenidone for patients with mild-to-moderate IPF, defined as FVC > 50% predicted and DLCO > 35% predicted 1, 3

Practical Considerations

• Smoking should be discontinued prior to and during treatment with pirfenidone as it increases drug metabolism 1, 3
• Patients on pirfenidone should be warned about UV exposure due to photosensitivity risk 1, 3
• Liver function tests should be performed prior to initiation of pirfenidone, monthly for the first 6 months, and every 3 months thereafter 1, 3
• Concomitant use of omeprazole with pirfenidone should be avoided as it may alter pirfenidone pharmacokinetics 1

Combination Therapy

• Combination therapy with nintedanib and add-on pirfenidone has a manageable safety profile but with increased gastrointestinal adverse events (69.8% vs 52.9% with nintedanib alone) 5
• For patients with SARD-ILD receiving mycophenolate without evidence of ILD progression, adding nintedanib or pirfenidone is conditionally recommended against 1
• Upfront combination of nintedanib or pirfenidone with mycophenolate over mycophenolate alone as first-line treatment is conditionally recommended against 1

Treatment Algorithm

1. Initial Assessment:

   • Confirm IPF diagnosis through high-resolution CT and/or surgical lung biopsy 1
   • Assess disease severity using pulmonary function tests (FVC, DLCO) 1, 3

2. First-line Treatment Selection:

   • For mild-to-moderate IPF (FVC > 50% predicted, DLCO > 35% predicted):
     • Nintedanib 150mg twice daily is preferred due to better mortality outcomes 2
     • Pirfenidone (titrated to 801mg three times daily) is an alternative if nintedanib is not tolerated 1

3. Monitoring:

   • Regular assessment of clinical tolerance and disease progression 3
   • For pirfenidone: liver function tests monthly for first 6 months, then every 3 months 1, 3
   • For nintedanib: monitor for diarrhea and other gastrointestinal symptoms 4, 2

4. Dose Adjustments:

   • If nintedanib is not tolerated at 150mg twice daily, reduce to 100mg twice daily 1
   • If pirfenidone is not tolerated, reduce dose as needed 1

5. Treatment of Disease Progression:

   • Consider switching to the alternative agent if progression occurs despite treatment 1
   • Consider referral for lung transplantation evaluation in appropriate candidates 1