What is the role of Nintedanib (BIBF 1120) in treating Interstitial Lung Disease (ILD) with Lupus Nephritis in patients with Systemic Lupus Erythematosus (SLE)?

Nintedanib in SLE with ILD and Lupus Nephritis

Nintedanib is not recommended as a first-line treatment for interstitial lung disease (ILD) in patients with systemic lupus erythematosus (SLE), particularly those with lupus nephritis. 1

Treatment Recommendations for SLE-ILD with Lupus Nephritis

First-Line Treatment Options

• Glucocorticoids: Conditionally recommended as first-line therapy for SLE-ILD 1

  • Typically oral prednisone for maintenance
  • IV pulse methylprednisolone for acute or severe presentations

• Immunosuppressive Agents: Conditionally recommended as first-line options 1

  • Mycophenolate: Preferred for patients with concurrent lupus nephritis
  • Cyclophosphamide: Particularly effective for severe ILD with lupus nephritis
  • Rituximab: Alternative option for refractory cases
  • Azathioprine: Can be used for maintenance therapy

Role of Nintedanib in SLE-ILD

Nintedanib has no established role in SLE-ILD based on current guidelines. The 2023 ACR/CHEST guidelines specifically:

• Conditionally recommend against nintedanib as first-line treatment for ILD associated with systemic autoimmune rheumatic diseases (SARDs) other than systemic sclerosis (SSc) 1
• Do not mention nintedanib as a treatment option specifically for SLE-ILD 1
• Only conditionally recommend nintedanib for:
  • SSc-ILD as a first-line option 1
  • SARD-ILD progression despite first-line treatment 1

Special Considerations for Lupus Nephritis

For patients with concurrent lupus nephritis:

• Mycophenolate is particularly advantageous as it treats both nephritis and ILD 1
• Cyclophosphamide may be considered for severe manifestations of both conditions 1
• Nintedanib has no established role in treating lupus nephritis and could potentially complicate management due to:
  • Lack of efficacy data in SLE-ILD
  • No effect on extrapulmonary manifestations of SLE 1
  • Potential adverse effects (especially diarrhea) that could worsen quality of life 2

Treatment Algorithm for SLE-ILD with Lupus Nephritis

1. Initial Assessment:

   • Determine ILD pattern and severity via HRCT and PFTs
   • Assess lupus nephritis activity via renal function tests and urinalysis

2. First-Line Treatment:

   • Start glucocorticoids (typically prednisone 0.5-1 mg/kg/day) 1
   • Add mycophenolate (preferred) or cyclophosphamide (for severe disease) 1

3. Monitoring Response:

   • Follow pulmonary function tests every 3-6 months
   • Monitor renal function and proteinuria
   • Assess for clinical improvement in respiratory symptoms

4. For Progressive Disease Despite First-Line Treatment:

   • Consider switching immunosuppressants (e.g., from mycophenolate to cyclophosphamide or rituximab) 1
   • Only then consider adding nintedanib as a second-line option for progressive fibrosing ILD 1, 3

Important Caveats

• Nintedanib primarily slows FVC decline rather than providing stabilization or improvement 1
• The INBUILD trial demonstrated nintedanib's efficacy in progressive fibrosing ILDs, but SLE-ILD was not specifically studied 3
• Nintedanib has no effect on extrapulmonary manifestations of SLE, including lupus nephritis 1
• Common adverse effects include diarrhea, which can significantly impact quality of life 2
• Nintedanib requires regular monitoring, including monthly liver function tests for the first 6 months 2

The management of SLE-ILD with lupus nephritis should focus on immunosuppressive therapies that address both pulmonary and renal manifestations, with nintedanib reserved only for cases with progressive fibrotic ILD despite optimal immunosuppressive therapy.