Nintedanib in Interstitial Lung Disease with Chronic Kidney Disease

Efficacy of Nintedanib in ILD

Nintedanib is an intracellular inhibitor of multiple tyrosine kinases that targets growth factor receptors including vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) 1
In progressive pulmonary fibrosis (PPF), nintedanib significantly reduces the annual rate of forced vital capacity (FVC) decline by approximately 107 ml compared to placebo 2, 3
The efficacy varies by underlying disease type, with greater FVC preservation in CTD-related ILD (106.2 ml/yr), fibrotic NSIP (141.7 ml/yr), and fibrotic occupational lung disease (252.8 ml/yr) 2, 3
Nintedanib decreases the risk of ILD progression 2.4 times in patients with progressive pulmonary fibrosis 2, 3

Gastrointestinal effects are most common with nintedanib treatment, including diarrhea (2.8 times more frequent than placebo), abdominal pain (4.2 times more frequent), nausea (3.1 times more frequent), vomiting (3.6 times more frequent), anorexia (2.8 times more frequent), and weight loss (3.7 times more frequent) 2, 3
Liver enzyme elevations are also common, including elevated aspartate aminotransferase (3.2 times more frequent) and elevated alanine aminotransferase (3.6 times more frequent) 2, 3
Nintedanib increases the likelihood of any adverse event (1.1 times more frequent), adverse events leading to permanent dose reduction (7.9 times more frequent), and adverse events leading to treatment discontinuation (1.9 times more frequent) 2, 3

The standard dose of nintedanib is 150mg twice daily, but dose reduction to 100mg twice daily should be considered if not tolerated in patients with renal impairment 4
For persistent diarrhea or other significant adverse effects, temporary dose reduction to 100 mg twice daily or treatment interruption may be necessary 1, 4
Liver function tests should be performed regularly as nintedanib can cause elevations in liver enzymes 2, 3, 4

Confirm ILD diagnosis and assess severity (FVC, DLCO, radiological pattern) 2, 3
Start nintedanib at standard dose of 150 mg twice daily for patients with mild to moderate CKD (creatinine clearance > 30 mL/min) 1, 4
Consider starting at reduced dose of 100 mg twice daily with careful monitoring for patients with severe CKD (creatinine clearance < 30 mL/min) 4

The quality of evidence for nintedanib in PPF is rated as low to moderate, meaning that the committee had low confidence in the estimated effects 2, 3, 5
Nintedanib slows disease progression but does not reverse existing fibrosis 4

The American College of Rheumatology recommends nintedanib for patients with a UIP pattern of ILD, irrespective of the underlying systemic autoimmune rheumatic disease, with a strength of evidence rated as low to moderate 6, 7
Nintedanib is conditionally recommended as a first-line option for systemic sclerosis-ILD, though immunosuppressive medications are preferred, with a strength of evidence rated as low to moderate 6, 7
For patients with RA-ILD with a fibrotic/UIP pattern, some panelists consider nintedanib as first-line therapy, though no consensus was reached, with a strength of evidence rated as low to moderate 6, 7
Nintedanib is generally conditionally recommended against as first-line therapy for other autoimmune ILDs, except when a UIP pattern is present, with a strength of evidence rated as low to moderate 6, 7
Combination therapy with nintedanib and mycophenolate is generally recommended against in patients without evidence of progression due to cost, adverse effects, and limited efficacy data, with a strength of evidence rated as low to moderate 6, 7