Fig. 1
From: Exposure–safety analyses of nintedanib in patients with chronic fibrosing interstitial lung disease
Expected percentage of patients having a liver enzyme elevation for different nintedanib plasma exposure levels (Cpre,ss) after 1 year of treatment based on the final exposure–liver enzyme elevation model, using pooled data from trials in IPF, SSc-ILD and progressive fibrosing ILD other than IPF (TOMORROW, INPULSIS, SENSCIS and INBUILD). A, B Final liver enzyme elevation model based on 2014 references ranges of ALT and AST used for the INBUILD primary analysis. The figure is stratified by combined IPF and SSc-ILD trials (TOMORROW, INPULSIS, SENSCIS) versus the trial in progressive fibrosing ILDs other than IPF (INBUILD) C Sensitivity analysis with 2019 updated reference ranges of ALT and AST in the INBUILD trial (study effect removed). The solid lines represent the expected percentage of patients with liver enzyme elevations based on point estimates of the final liver enzyme elevation model. The shaded areas represent the 95% CI based on 2000 bootstrap replicates. The black-filled circle indicates the median Cpre,ss in patients receiving 150 mg nintedanib BID in TOMORROW, INPULSIS-1/2, SENSCIS and INBUILD. The dashed grey line indicates the 5th and 95th percentiles of Cpre,ss. A Final exposure–liver enzyme elevation model: IPF and SSc-ILD trials (TOMORROW, INPULSIS, SENSCIS), B Final exposure–liver enzyme elevation model: progressive fibrosing ILD trial (INBUILD). C Sensitivity analysis (use of 2019 updated reference ranges of ALT and AST for INBUILD and study effect removed): trials in IPF, SSc-ILD and progressive fibrosing ILD other than IPF (TOMORROW, INPULSIS, SENSCIS, INBUILD). AST aspartate transaminase, ALT alanine transaminase, BID twice daily, CI confidence interval, Cpre,ss pre-dose drug concentration in plasma at steady state, ILD interstitial lung disease, IPF idiopathic pulmonary fibrosis, SSc-ILD systemic sclerosis-associated interstitial lung disease