Nintedanib Treatment for Interstitial Lung Disease

Introduction to Nintedanib Indications

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), as recommended by the European Respiratory Society 1, 2

The American Thoracic Society recommends nintedanib (150mg twice daily) as a first-line treatment option for SSc-ILD, either alone or in combination with mycophenolate mofetil (MMF) 1, 3
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), according to the American College of Rheumatology 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), as reported by the European League Against Rheumatism 1
Nintedanib is indicated for patients with PF-ILD who have failed standard management for fibrotic ILD, as stated by the American Thoracic Society 4
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, according to the American Journal of Respiratory and Critical Care Medicine 4

The standard dose of nintedanib is 150mg twice daily, as recommended by the European Respiratory Society 2, 4
The dose can be reduced to 100mg twice daily if not tolerated, according to the American College of Rheumatology 2

In SSc-ILD, nintedanib reduced annual FVC decline by 44% compared to placebo in the SENSCIS trial, as reported by the American Thoracic Society 1, 3
In PF-ILD, nintedanib reduced FVC decline by 102.7 mL/year compared to placebo (p=0.012) among 170 patients with autoimmune disease-related ILDs in the INBUILD trial, according to the American Journal of Respiratory and Critical Care Medicine 1

Diarrhea is the most common adverse event (75.7% of patients in the nintedanib group vs. 31.6% in placebo), as reported by the European League Against Rheumatism 1
Other common gastrointestinal adverse effects include abdominal pain, nausea, vomiting, anorexia, and weight loss, according to the American Thoracic Society 4
Liver enzyme elevations (AST, ALT) are also common, as stated by the American Journal of Respiratory and Critical Care Medicine 4
Management strategies include dose reduction to 100mg twice daily if not tolerated, as recommended by the American College of Rheumatology 2
Regular monitoring of liver function is also recommended, according to the American Thoracic Society 4

Nintedanib slows disease progression but does not reverse existing fibrosis, as reported by the European Respiratory Society 1, 4
It has no effect on non-ILD manifestations of systemic autoimmune rheumatic diseases, according to the American College of Rheumatology 5
For patients already on mycophenolate without evidence of ILD progression, adding nintedanib is conditionally not recommended, as stated by the American Thoracic Society 5, 6

For patients with SSc-ILD, consider nintedanib (150mg twice daily) alone or with MMF, as recommended by the European League Against Rheumatism 1, 3
Alternative options include MMF, rituximab, cyclophosphamide, or tocilizumab, according to the American College of Rheumatology 1, 7
Strongly avoid daily glucocorticoids as first-line treatment, as stated by the American Thoracic Society 7

The American College of Rheumatology and the American College of Chest Physicians conditionally recommend nintedanib for SSc-ILD progression despite first-line immunosuppressive therapy, defined as a decline in FVC ≥5-10% predicted, worsening respiratory symptoms, or increased fibrosis on HRCT, in patients with systemic sclerosis @8
Progressive ILD is defined as FVC decline ≥10% predicted within 24 months, or FVC decline 5-10% predicted plus worsening respiratory symptoms or increased fibrosis on HRCT, or worsening respiratory symptoms and increased fibrosis on HRCT @8
Residual changes alone on HRCT do not equal progression, and comparison to baseline HRCT is necessary to determine if fibrosis has increased @9

The American College of Rheumatology conditionally recommends adding nintedanib 150 mg twice daily to the existing MMF regimen in patients with documented progression of ILD @8
In patients without clear progression, the American College of Rheumatology conditionally recommends against adding nintedanib to mycophenolate @8, 10
Patients without clear progression should continue MMF alone and be monitored closely with repeat PFTs every 3-6 months and HRCT within 6 months to detect early progression @8, 9, 10

The first 3 years after diagnosis are critical for identifying progressive disease @9
Strongly avoid glucocorticoids in SSc-ILD due to increased risk of scleroderma renal crisis, particularly at doses >15 mg/day prednisone equivalent @8, 11
Consider early lung transplant referral if disease continues to progress despite combination therapy @8
Continue monitoring PFTs every 3-6 months to assess treatment response after starting nintedanib @9