What is the role of Nintedanib in treating Idiopathic (Interstitial) Lung Disease (ILD) with Non-Specific Interstitial Pneumonia (NSIP)?

From the Guidelines

Nintedanib is conditionally recommended for the treatment of Idiopathic Interstitial Lung Disease (ILD) with Non-Specific Interstitial Pneumonia (NSIP) progression after first ILD therapy, based on the 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline 1. To implement this treatment:

• Start with 150 mg twice daily, as this is the typical dosage for nintedanib in the treatment of ILD.
• Monitor for side effects, particularly gastrointestinal issues, as nintedanib can cause diarrhea, nausea, and abdominal pain.
• If side effects occur, the dose can be reduced to 100 mg twice daily, to minimize adverse effects while maintaining therapeutic efficacy.
• Continue treatment indefinitely, as nintedanib is used for long-term management of ILD, and its benefits in slowing disease progression have been established 1. Key considerations for nintedanib treatment include:
• Regular monitoring of liver function tests, as nintedanib can cause liver enzyme elevations.
• Caution in patients with a history of bleeding or those on anticoagulation therapy, as nintedanib can increase the risk of bleeding.
• Patient education on potential side effects and the importance of adherence to treatment, to ensure optimal outcomes and minimize complications. The use of nintedanib in ILD with NSIP is supported by the most recent guideline evidence, which conditionally recommends its use in patients with disease progression after first-line therapy 1.

From the Research

Role of Nintedanib in Treating Idiopathic (Interstitial) Lung Disease (ILD) with Non-Specific Interstitial Pneumonia (NSIP)

• Nintedanib has been approved for the treatment of chronic fibrosing ILD with a progressive phenotype, including idiopathic non-specific interstitial pneumonia, based on the data from the INBUILD trial 2.
• The INBUILD trial showed that nintedanib slowed the annual decline of pulmonary function by 57% in patients with chronic hypersensitivity pneumonitis, idiopathic non-specific interstitial pneumonia, unclassifiable ILD, autoimmune ILD, sarcoidosis, and others 2.
• Nintedanib can inhibit processes involved in the progression of fibrosis and can reduce the decline in forced vital capacity in patients with idiopathic pulmonary fibrosis (IPF) and fibrotic-interstitial lung disease (fibrotic-ILDs) 3.
• The safety of nintedanib for the treatment of interstitial lung disease has been evaluated in a systematic review and meta-analysis of randomized controlled trials, which showed that patients treated with nintedanib had a significantly higher likelihood of having any adverse events or adverse events leading to treatment discontinuation 3.
• The management of patients with fibrotic, progressive, and immunosuppressive treatment-refractory NSIP remains uncertain, and further studies are needed to address the role of antifibrotic drugs in this setting 4.

Adverse Events Associated with Nintedanib

• The use of nintedanib is positively associated with diarrhea, nausea, vomiting, and weight loss 3.
• Patients treated with nintedanib were less likely to have a cough and dyspnea 3.

Current Treatment Landscape for ILD

• Antifibrotic agents, such as nintedanib and pirfenidone, have revolutionized the treatment landscape of patients with idiopathic pulmonary fibrosis (IPF) 5.
• The approval of nintedanib has also expanded the therapeutic options for patients with progressive pulmonary fibrosis other than IPF 5.
• Current therapeutic strategies based on antifibrotic agents and/or immunomodulation are associated with non-negligible side effects, and several studies have explored the inhalation route aiming to spread higher local concentrations while limiting systemic toxicity 5.