Pulmonary fibrosis can develop in a wide range of heterogeneous interstitial lung diseases (ILDs) from different etiologies. As fibrosis increases from mild to severe, patients may experience progressive loss of lung function with worsening respiratory symptoms.^1-5

The accumulation of fibrosis in the interstitium leads to the irreversible distortion of lung architecture and increased lung tissue stiffness, which results in impaired gas exchange and pulmonary function.^1,7

Although ILDs differ in etiology, common pathways leading to fibrosis may be shared. The fibrotic response can be initiated by inflammation or chronic tissue injury and is influenced by the coagulation cascade. Mediated through fibroblast proliferation, migration, and differentiation, this cycle of abnormal repair may become self-sustaining and lead to irreversible damage.^1-4,7-9

Invading fibroblasts and myofibroblasts evade apoptosis while continuing to release ECM, and potentially inhibit its breakdown, leading to excessive deposition.^1,2,7

Nintedanib is a small molecule, multi-targeted inhibitor of receptor tyrosine kinases (RTKs) PDGFR, FGFR, VEGFR, and CSF1R that are involved in the pathogenesis of lung fibrosis. Nintedanib also inhibits FLT-3 and non-receptor tyrosine kinases (nRTKs) such as Lck, Lyn, and Src kinases. The contribution of FLT-3 and nRTK inhibition to nintedanib efficacy in ILD is unknown. Nintedanib has a proven mechanism of action and has been shown to inhibit fibroblast proliferation, migration, and fibroblast-to-myofibroblast transformation.^10-12
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