Which lung diseases can be treated with nintedanib?

Lung Diseases Treatable with Nintedanib

Nintedanib is approved for three primary lung disease categories: idiopathic pulmonary fibrosis (IPF), systemic sclerosis-associated interstitial lung disease (SSc-ILD), and progressive fibrosing interstitial lung diseases (PF-ILD) of various etiologies. 1

FDA-Approved Indications

1. Idiopathic Pulmonary Fibrosis (IPF)

• Nintedanib at 150 mg twice daily is strongly recommended for all patients with confirmed IPF, regardless of disease severity, to slow functional decline. 1
• The drug reduces annual FVC decline by approximately 125 mL compared to placebo, demonstrating meaningful preservation of lung function. 1
• Treatment should be initiated early in the disease course to maximize lung function preservation. 1
• IPF diagnosis must be confirmed using the 2022 ATS/ERS criteria with high-resolution CT and/or lung biopsy showing usual interstitial pneumonia (UIP) pattern. 1

2. Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD)

• Nintedanib (150 mg twice daily) should be considered either as monotherapy or in combination with mycophenolate mofetil for SSc-ILD. 2, 3
• In the SENSCIS trial, nintedanib reduced the adjusted annual FVC decline to -52.4 mL/year versus -93.3 mL/year with placebo (p=0.04). 2, 3
• The treatment effect is consistent regardless of concurrent mycophenolate use: 26.3 mL/year additional FVC preservation when combined with mycophenolate versus 55.4 mL/year when used alone. 2, 3
• The adverse event profile remains similar whether nintedanib is used alone or with mycophenolate. 2

3. Progressive Fibrosing Interstitial Lung Disease (PF-ILD)

• Nintedanib is conditionally recommended for any progressive fibrosing ILD that meets specific progression criteria, making it the only antifibrotic with formal endorsement for non-IPF progressive fibrosing ILDs. 1

Defining Progressive Fibrosing ILD

PF-ILD is diagnosed when patients demonstrate at least two of the following three criteria within the past 12-24 months: 1

• Worsening respiratory symptoms (increased dyspnea or cough)
• FVC decline ≥10% predicted, OR FVC decline 5-10% predicted plus worsening symptoms or radiological progression
• Radiological progression on HRCT (new or increased traction bronchiectasis, ground-glass opacity with traction bronchiectasis, reticulation, honeycombing, or lobar volume loss)

Specific PF-ILD Subtypes That Respond to Nintedanib

The INBUILD trial demonstrated efficacy across multiple autoimmune and fibrotic ILDs: 2

• Connective tissue disease-related ILD (106.2 mL/year FVC preservation) 1
• Fibrotic non-specific interstitial pneumonia (NSIP) (141.7 mL/year FVC preservation) 1
• Fibrotic occupational lung disease (252.8 mL/year FVC preservation) 1
• Rheumatoid arthritis-related ILD with UIP pattern 4
• Chronic hypersensitivity pneumonitis 5
• Sarcoidosis with progressive fibrosis 5
• Unclassifiable interstitial pneumonia 5

Among 170 patients with autoimmune disease-related ILDs in INBUILD, nintedanib reduced FVC decline by 102.7 mL/year compared to placebo (p=0.012). 2

Dosing and Administration Algorithm

Standard Dosing

• Start all eligible patients on 150 mg orally twice daily—this is the evidence-based dose that demonstrated efficacy in clinical trials. 1
• Dose reduction to 100 mg twice daily should be reserved only for patients who cannot tolerate the standard dose due to adverse effects, particularly gastrointestinal symptoms. 1, 3

Monitoring Protocol

First 3 months: 1

• Monthly liver enzyme tests (AST/ALT)
• Monthly assessment for diarrhea and weight loss
• Monthly body weight measurement

After month 3: 1

• Liver enzyme monitoring every 3 months
• Pulmonary function tests every 3-6 months
• Ongoing surveillance for gastrointestinal symptoms and weight changes

Adverse Effects and Management

Gastrointestinal Effects (Most Common)

• Diarrhea occurs in approximately 62-76% of patients on nintedanib versus 18-32% on placebo. 1, 3
• Nausea is 3.1-fold more frequent. 1
• Vomiting is 3.6-fold more frequent. 1
• Abdominal pain is 4.2-fold more frequent. 1
• Weight loss is 3.7-fold more frequent. 1

Management strategy: For persistent diarrhea, reduce dose to 100 mg twice daily—this manages symptoms in most patients without requiring discontinuation. 1

Hepatotoxicity

• AST elevation is 3.2-fold more common. 1
• ALT elevation is 3.6-fold more common. 1
• Serious liver enzyme and bilirubin elevations occur at a rate of 4.0 per 1000 patient-years. 6
• If liver enzymes do not resolve after dose reduction, permanent discontinuation may be warranted. 1

Treatment Discontinuation Rates

• Permanent dose reduction is required 7.9-fold more often with nintedanib than placebo. 1
• Overall treatment discontinuation occurs 1.9-fold more frequently. 1

Critical Clinical Considerations

Combination Therapy

• For SSc-ILD, nintedanib can be safely combined with mycophenolate mofetil with similar adverse event profile to nintedanib alone. 2, 1
• For patients already on mycophenolate without evidence of ILD progression, adding nintedanib is conditionally not recommended due to cost, adverse effects, and limited efficacy data. 4, 3

Supportive Care

• Aggressively manage gastroesophageal reflux disease with proton pump inhibitors to mitigate gastrointestinal complications. 1, 3
• Promptly treat respiratory infections. 1
• Consider pulmonary rehabilitation. 1

Important Limitations

• Nintedanib slows disease progression but does not reverse existing fibrosis. 4, 3
• It has no effect on non-ILD manifestations of systemic autoimmune rheumatic diseases. 3
• The quality of evidence for nintedanib in PF-ILD is rated as low to moderate. 1, 4

Common Pitfall to Avoid

Do not delay treatment initiation or discontinue prematurely for diarrhea without first attempting dose reduction to 100 mg twice daily. 1 Most patients can continue treatment with appropriate dose adjustment and supportive management.