What is the indication for Nintedanib (generic name) in Interstitial Lung Disease (ILD)?

Indications for Nintedanib in Interstitial Lung Disease

Nintedanib is indicated for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD) and progressive fibrosing interstitial lung disease (PF-ILD), where it slows the rate of decline in forced vital capacity (FVC). 1

Specific Indications by ILD Type

SSc-ILD

• Nintedanib (150mg twice daily) is recommended as a first-line treatment option for SSc-ILD, either alone or in combination with mycophenolate mofetil (MMF) 1
• In the SENSCIS trial, nintedanib reduced the annual rate of FVC decline to -52.4 mL/year compared to -93.3 mL/year with placebo (p=0.04) 1
• The treatment effect was consistent regardless of concomitant MMF use (40% reduction in FVC decline for those taking MMF at baseline and 46% for those not using) 1

Progressive Fibrosing ILD (PF-ILD)

• Nintedanib is indicated for patients with PF-ILD who have failed standard management for fibrotic ILD 1
• The INBUILD trial demonstrated that nintedanib slowed FVC decline in patients with various progressive fibrosing ILDs, with a difference of 107 mL/year compared to placebo 1, 2
• PF-ILD includes various ILDs that show progression with fibrosis measured by FVC decline, worsening high-resolution CT findings, and respiratory symptoms 2

Other SARD-ILDs

• For rheumatoid arthritis-associated ILD (RA-ILD), expert opinion is divided, with no consensus on nintedanib as first-line therapy 1
• For Sjögren's disease-ILD (SjD-ILD), inflammatory myopathy-ILD (IIM-ILD), and mixed connective tissue disease-ILD (MCTD-ILD), nintedanib is conditionally not recommended as first-line treatment 1

Dosing and Administration

• Standard dose: 150mg twice daily 1
• Can be reduced to 100mg twice daily if not tolerated 1
• May be used alone or in combination with MMF in SSc-ILD 1

Efficacy Evidence

• In SSc-ILD: Reduced annual FVC decline by 44% compared to placebo in the SENSCIS trial 1
• In PF-ILD: Among 170 patients with autoimmune disease-related ILDs in the INBUILD trial, nintedanib reduced FVC decline by 102.7 mL/year compared to placebo (p=0.012) 1
• Efficacy appears consistent across Japanese and non-Japanese populations with SSc-ILD 3

Adverse Effects and Management

• Diarrhea is the most common adverse event (75.7% of patients in the nintedanib group vs. 31.6% in placebo) 1
• Other common gastrointestinal adverse effects include abdominal pain, nausea, vomiting, anorexia, and weight loss 1
• Liver enzyme elevations (AST, ALT) are also common 1
• Management strategies include:
  • Dose reduction to 100mg twice daily if not tolerated 1
  • Combination of diet adjustment, probiotics, and diosmectite for gastrointestinal side effects 4
  • Regular monitoring of liver function 1

Important Considerations

• Nintedanib slows disease progression but does not reverse existing fibrosis 1
• It has no effect on non-ILD manifestations of systemic autoimmune rheumatic diseases 1
• For patients already on mycophenolate without evidence of ILD progression, adding nintedanib is conditionally not recommended 1
• Upfront combination of nintedanib with mycophenolate is conditionally not recommended over mycophenolate alone as first-line treatment 1

Treatment Algorithm for SSc-ILD

1. For patients with SSc-ILD:

   • Consider nintedanib (150mg twice daily) alone or with MMF 1
   • Alternative options include MMF, rituximab, cyclophosphamide, or tocilizumab 1
   • Strongly avoid daily glucocorticoids as first-line treatment 1

2. For patients with other forms of PF-ILD:

   • Consider nintedanib after failure of standard management 1
   • Standard management may include immunosuppression, antigen remediation, or observation depending on the underlying ILD 1

3. Monitor treatment response:

   • Follow FVC trends over time 1
   • Assess for adverse effects, particularly gastrointestinal symptoms and liver function abnormalities 1
   • Consider dose reduction to 100mg twice daily if adverse effects are significant 1