Nintedanib in the management of idiopathic pulmonary fibrosis: clinical trial evidence and real-world experience

Abstract

Idiopathic pulmonary fibrosis (IPF) is a fibrotic interstitial lung disease associated with significant morbidity and mortality. Previously, IPF has been managed using immunosuppressive therapy; however, it has been shown that this is associated with increased mortality. In the last 5 years, two disease-modifying agents have been licensed for use in IPF, namely pirfenidone and nintedanib. Nintedanib is a tyrosine kinase inhibitor with antifibrotic properties that has also been shown to significantly reduce the progression of the disease. The scientific evidence shows that nintedanib is effective and well tolerated for the treatment of IPF in mild, moderate and severe stages of the disease. Real-world experiences also support the findings of previously conducted clinical trials and show that nintedanib is effective for the management of IPF and is associated with reducing disease progression. Gastrointestinal events, mainly diarrhoea, are the main adverse events caused by the treatment. Recent real-word studies also suggest that nintedanib stabilizes lung function till lung transplantation, with no increased surgical complications or postoperative mortality after lung transplantation. In this review, we will discuss the clinical trial evidence and real-world experience for nintedanib in the management of IPF.

Eupatilin treatment inhibits transforming growth factor beta-induced endometrial fibrosis in vitro

“…Furthermore, Ning et al [2] reported that down-regulation of miRNA-326 was strongly associated with intrauterine adhesion, characterized by endometrial fibrosis and high levels of TGF-β1, α-SMA, COL1A1, and fibronectin, as we observed in the present study. Recently, two small molecules (pirfenidone and nintedanib) were approved for idiopathic pulmonary disease, as they showed combinatorial anti-inflammatory, antioxidant, and antifibrotic effects [24,25]. Moreover, Kim et al [18] reported that eupatilin treatment attenuated the progression of bleomycin-induced lung fibrosis and TGF-β-induced fibrotic activity in hepatic stellate cells by disturbing Smad3 phosphorylation, which subsequently led to myofibroblast dedifferentiation and reversal of fibrotic progression.…”

Bad Neighborhood: Fibrotic Stroma as a New Player in Melanoma Resistance to Targeted Therapies

“…Nintedanib (BIBF1120), an inhibitor of PDGFR, vascular endothelial growth factor receptor (VEGFR), and fibroblast growth factor receptor 1 (FGFR1), was initially studied for its role in angiogenesis inhibition, but its importance in the treatment of fibrotic disease derives from the ability to suppress myofibroblast differentiation and to reduce collagen deposition [111]. Recent clinical trials have shown the efficacy and tolerability of Nintedanib in lung fibrosis treatment [112,113]. Moreover, it has been shown that in combination with traditional chemotherapy, BIBF1120 improves clinical outcomes in terms of response rate and progression-free survival in non-small cell lung cancer patients [114,115].…”

Ongoing challenges in pulmonary fibrosis and insights from the nintedanib clinical programme

“…Two pharmacological therapies (nintedanib and pirfenidone) have been shown to slow decline in lung function in patients with IPF [1][2][3][4][5]. The United States Food and Drug Administration and European Medicines Agency approvals of nintedanib and pirfenidone changed the treatment paradigm in IPF and increased understanding of the underlying disease mechanisms [5]. However, these approvals raised new questions in the management of ILD, and prior unmet needs remain to be addressed.…”