Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor 
prognosis. The molecular mechanisms involved in the progression of IPF are not 
fully understood; however, the platelet-derived growth factor (PDGF)/PDGF 
receptor pathway is thought to play a critical role in fibrogenesis of the 
lungs. Other growth factors, including fibroblast growth factor and vascular 
endothelial growth factor, are also thought to contribute to the pathogenesis of 
pulmonary fibrosis. Nintedanib is an inhibitor of multiple tyrosine kinases, 
including receptors for PDGF, fibroblast growth factor, and vascular endothelial 
growth factor. In the Phase II TOMORROW trial, treatment with 150 mg of 
nintedanib twice daily showed a trend to slow the decline in lung function and 
significantly decrease acute exacerbations in patients with IPF, while showing 
an acceptable safety profile. The Phase III INPULSIS trials demonstrated a 
significant decrease in the annual rate of decline in forced vital capacity in 
IPF patients treated with 150 mg nintedanib twice daily. In the INPULSIS-2 
trial, the time to the first acute exacerbation significantly increased in IPF 
patients who were treated with 150 mg of nintedanib twice daily. Pirfenidone, 
another antifibrotic drug, was shown to limit the decline in pulmonary function 
in patients with IPF in the ASCEND trial. Combination therapy with nintedanib 
and pirfenidone is anticipated, although further evaluation of its long-term 
safety is needed. There is limited evidence for the safety of the combination 
therapy although a Phase II trial conducted in Japan demonstrated that 
combination therapy with nintedanib and pirfenidone was tolerable for 1 month. 
Available antifibrotic agents (ie, pirfenidone and N-acetylcysteine) have 
limited efficacy as single therapies for IPF; therefore, further study of 
combination therapy with antifibrotic agents is needed.