Indications for Nintedanib
Nintedanib is FDA-approved for three primary indications: idiopathic pulmonary fibrosis (IPF), systemic sclerosis-associated interstitial lung disease (SSc-ILD), and chronic fibrosing interstitial lung diseases with a progressive phenotype (progressive pulmonary fibrosis). 1, 2
FDA-Approved Fibrotic Lung Disease Indications
Idiopathic Pulmonary Fibrosis (IPF)
- Nintedanib at 150 mg twice daily is approved for all patients with confirmed IPF diagnosis, regardless of disease severity 1
- The drug reduces the annual rate of FVC decline by approximately 125 mL compared to placebo 1, 3
- Nintedanib reduces the risk of acute exacerbations of IPF (HR 0.16; 95% CI, 0.04-0.70) 1
- Treatment should be initiated early in the disease course to preserve lung function 1
Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD)
- Nintedanib is approved for SSc-ILD at 150 mg twice daily, either as monotherapy or in combination with mycophenolate mofetil 4
- In the SENSCIS trial, nintedanib reduced the adjusted annual rate of FVC decline to -52.4 mL per year versus -93.3 mL per year with placebo (p=0.04) 4
- The treatment effect was consistent regardless of concurrent mycophenolate use: 26.3 mL/year benefit with mycophenolate versus 55.4 mL/year without it 4, 1
- The American College of Rheumatology recommends nintedanib for SSc-ILD with a UIP pattern, though immunosuppressive medications are generally preferred as first-line 5
Progressive Pulmonary Fibrosis (PF-ILD)
- Nintedanib is approved for chronic fibrosing ILDs with a progressive phenotype, defined by FVC decline ≥10% predicted within 24 months, or FVC decline 5-10% predicted plus worsening respiratory symptoms or increased fibrosis on imaging within 24 months 1
- In the INBUILD trial, nintedanib reduced annual FVC decline by approximately 107 mL compared to placebo across various progressive ILDs 1, 5
- The benefit varies by underlying disease: CTD-related ILD (106.2 mL/yr), fibrotic NSIP (141.7 mL/yr), and fibrotic occupational lung disease (252.8 mL/yr) 1, 5
- Nintedanib decreases the risk of ILD progression 2.4-fold in progressive pulmonary fibrosis 1, 5
Non-Small Cell Lung Cancer Indication
Advanced Adenocarcinoma NSCLC (Second-Line)
- In the European Union, nintedanib at 200 mg twice daily is approved in combination with docetaxel as second-line therapy for patients with adenocarcinoma histology NSCLC who have progressed after first-line chemotherapy 1, 2
- This indication is based on differential clinical benefits observed in adenocarcinoma versus squamous cell carcinoma histology 6
- Nintedanib selectively inhibits tumor-associated fibroblasts in adenocarcinoma, which may explain the histology-specific benefit 6
Important Dosing and Monitoring Considerations
Standard Dosing
- The approved therapeutic dose is 150 mg twice daily for all fibrotic ILD indications 1, 3
- Dose reduction to 100 mg twice daily should only be implemented for persistent adverse effects that cannot be managed with supportive care, particularly gastrointestinal symptoms 1, 3
Adverse Effect Profile
- Diarrhea occurs in approximately 62-76% of patients (versus 18-32% on placebo) 4, 1
- Gastrointestinal effects include nausea (3.1-fold increase), vomiting (3.6-fold), abdominal pain (4.2-fold), and weight loss (3.7-fold) 1, 5
- Liver enzyme elevations occur with AST elevated 3.2-fold and ALT elevated 3.6-fold more frequently than placebo 1, 5
- Adverse events lead to permanent dose reduction 7.9 times more frequently and treatment discontinuation 1.9 times more frequently than placebo 1, 5
Monitoring Protocol
- Obtain baseline liver function tests, body weight, and nutritional assessment 1
- Perform monthly liver enzyme tests for the first 3 months, then every 3 months thereafter 1, 3
- Monitor continuously for diarrhea, weight loss, and gastrointestinal symptoms 1, 3
- Implement aggressive GERD management with proton pump inhibitors and promptly treat respiratory infections 4, 1