LAUSR

Pirfenidone and nintedanib are the first two FDA-approved therapies for treatment of idiopathic pulmonary fibrosis (IPF). The clinical programs for pirfenidone and nintedanib included 1132 patients in the placebo arms and 1691 patients in the treatment arms across 6 trials. We developed a disease progression model to characterize the observed variability in lung function decline, measured as percent predicted forced vital capacity (%p-FVC), and its decrease in decline after treatment. The non-linear longitudinal change in %p-FVC was best described by a Weibull function. The median decreased decline in %p-FVC after treatment was estimated to be 1.50% (95% CI [1.12, 1.79]) and 1.96% (95% CI [1.47, 2.36]) at week 26 and week 52, respectively. Smoking status, weight, %p-FVC, %p-DLco and oxygen use at baseline were identified as significant covariates affecting decline in %p-FVC. The decreased decline in %p-FVC were observed among all subgroups of interest, of which the effects were larger at 1 year compared to 6 months. Based on the disease progression model smoking status and oxygen use at baseline may affect the treatment effect size. At week 52, the decreased decline in %p-FVC for current smokers and patients with oxygen use at baseline were 1.56 (90% CI [1.02, 1.99]) and 2.32 (90% CI [1.74, 2.86]), respectively. These prognostic factors may be used to enrich studies with patients who are more likely to respond to treatment, by demonstrating a lesser decline in lung function, and therefore provide the potential to allow for IPF studies with smaller study populations or shorter durations.