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American Thoracic Society (ATS) 2021
May 14, 2021 - May 19, 2021
Scott Siler, Chief Scientific Officer of DILIsym Services, Inc., to present, “Using Quantitative Systems Pharmacology Modeling to Understand the Pathophysiology of Idiopathic Pulmonary Fibrosis”
Patients with idiopathic pulmonary fibrosis (IPF) have a poor survival prognosis and limited treatment options. Underlying its clinical presentation is a complex pathophysiology. Mechanistic, mathematical modeling approaches such as quantitative systems pharmacology (QSP) can identify the links between pathophysiologic mechanisms and clinical sequela, aid in interpreting drug treatment results, and predict potential efficacy for novel treatments. One such QSP model, IPFsym, has recently been developed and has been applied to better understand IPF patient pathophysiology.
A simulated population (SimPops) of IPF patients was generated using the QSP model, IPFsym. Inter-patient variability in inflammation, epithelial cell health, fibroblasts, and collagen synthesis was introduced in accordance with published data. The resultant clinical presentation was also compared with published clinical data to ensure validity of SimPops. The response to simulated administration of nintedanib or pirfenidone was also predicted.
More than 700 simulated patients were generated within an IPF patient SimPops. The SimPops had appropriate ranges of alveolar epithelial cells (type I and II), macrophages, and myofibroblasts, in accordance with published data from IPF patients. The levels of extracellular matrix components were also consistent with clinical data, as were the fibroblastic foci and honeycombed lung volumes. Taken together, this pathophysiology generated a range of effects on respiration.
The validated IPF patient SimPops within IPFsym accurately describes various pathophysiologic mechanisms to produce FVC and DLCO outputs that decline as the patients simulate disease progression. Decline in respiratory function is predicted to be linked to the extent of honeycomb and fibroblastic foci lung volume. Moreover, the IPFsym SimPops can be used to investigate how modifying disease mechanisms with potential treatments can efficaciously reduce the rates of progression.