Can we give Nintedanib (BIBF 1120) to patients with hypersensitivity pneumonitis?

Nintedanib for Hypersensitivity Pneumonitis

Nintedanib can be recommended for patients with hypersensitivity pneumonitis who have developed a progressive fibrosing phenotype, as it has been shown to reduce the rate of lung function decline in progressive pulmonary fibrosis. 1

Rationale and Evidence

The American Thoracic Society and European Respiratory Society conditionally recommend nintedanib for progressive pulmonary fibrosis (PPF) in patients who have failed standard management for fibrotic interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF) 1. This recommendation extends to hypersensitivity pneumonitis with a progressive fibrosing phenotype.

Research evidence supports this approach:

• Nintedanib works by inhibiting multiple tyrosine kinases involved in fibrogenesis, blocking pathways that contribute to disease progression 1
• Laboratory studies demonstrate that nintedanib inhibits fundamental processes in fibrosis development regardless of the initial trigger, including in hypersensitivity pneumonitis models 2, 3
• In vitro studies specifically show that nintedanib counteracts fibrosing functions of lung fibroblasts derived from patients with progressive fibrosing hypersensitivity pneumonitis (PF-HP) 3

Dosing and Administration

• Standard dosing: 150 mg twice daily, approximately 12 hours apart with food 1
• Dose reduction to 100 mg twice daily may be necessary if not tolerated 1
• Treatment should be continued long-term as evidence suggests ongoing benefit 1

Monitoring Requirements

1. Liver function tests:

   • Monthly for the first 3 months
   • Every 3 months thereafter 1

2. Regular assessment of:

   • Disease progression
   • Symptoms
   • Weight loss
   • Dehydration 1

Expected Benefits

• Reduction in the annual rate of forced vital capacity (FVC) decline by approximately 100-125 mL compared to placebo 1
• Potential slowing of disease progression 1
• Note: Nintedanib slows but does not stop or reverse disease progression 1

Adverse Effects and Management

1. Gastrointestinal effects:

   • Diarrhea (occurs in 60-75% of patients)
   • Nausea and vomiting
   • Abdominal pain 1

2. Other common adverse effects:

   • Elevated liver enzymes (3.2-3.6 times more likely than placebo)
   • Weight loss 1

Most adverse effects do not lead to treatment discontinuation (<5% of patients) 1

Clinical Experience in Hypersensitivity Pneumonitis

A 3-year observational study of patients with fibrotic hypersensitivity pneumonitis treated with antifibrotics (including nintedanib) showed:

• Statistically significant annual decline in FVC % predicted of 4.2% (95% CI 1.9-6.6%)
• Decline in diffusing capacity (DLCO) % predicted of 5.7% (95% CI 3.1-8.4%) 4

While this indicates disease progression despite treatment, the rate of decline may be slower than would occur without treatment.

Important Considerations and Caveats

• Nintedanib is not recommended during acute exacerbations; it should be reserved for after resolution 1
• Not recommended in patients with moderate to severe hepatic impairment 1
• Elderly patients may have higher discontinuation rates 1
• Patients with mild hepatic impairment require close monitoring and potential dose adjustment 1
• Consider concomitant management of gastroesophageal reflux disease to prevent worsening of ILD due to aspiration 5

Conclusion

While more research is needed specifically for hypersensitivity pneumonitis, the available evidence supports the use of nintedanib in patients with progressive fibrosing hypersensitivity pneumonitis to slow the rate of lung function decline.