Parametric Time‐to‐Event Model for Acute Exacerbations in Idiopathic Pulmonary Fibrosis. (25th January 2020)

• Record Type: Journal Article
• Authors: Tang, Fei; Weber, Benjamin; Stowasser, Susanne; Korell, Julia
• Is Part Of: CPT: pharmacometrics & systems pharmacology. Volume 9:Number 2(2020)
• Page Start: 87
• Page End: 95
• Publication Date: 2020-01-25
• Subjects: Pharmacokinetics -- Periodicals; Pharmacology -- Periodicals; Pharmacokinetics; Periodicals; 615.05
• DOI: 10.1002/psp4.12485
• Languages: English
• ISSNs: 2163-8306

Abstract

Abstract : We describe a parametric time‐to‐event model for idiopathic pulmonary fibrosis (IPF) exacerbations and identify predictors of exacerbation risk using data obtained for the tyrosine‐kinase inhibitor nintedanib in two phase III studies (INPULSIS‐1/2). Parametric survival analysis was performed on time to first exacerbation (censoring on day 372), with univariate analysis to select statistically significant covariates ( P = 0.05). Multivariate covariate models were developed using stepwise covariate modeling with forward inclusion ( P = 0.05) and backward elimination ( P = 0.01). Sixty‐three first exacerbation events were reported across 1, 061 subjects in the INPULSIS studies. Baseline and decline of forced vital capacity (FVC)/percent‐predicted FVC (%pFVC), supplemental oxygen use, baseline CO diffusing capacity and age were statistically significant in the univariate analysis. The final covariate model included decline in FVC to week 52, baseline %pFVC, supplemental oxygen use, and age. The developed model may be used to identify patients at high risk of IPF exacerbations and accelerate development of novel treatments.