Background
Phase II trial data indicate that the preferential PDE4B inhibitor BI 1015550 prevents a decline in FVC over 12 weeks in patients with idiopathic pulmonary fibrosis (IPF).

Aims and objectives
Using Phase II trial data, we investigated the effect of BI 1015550 on gene expression profiles and their association with FVC.

Methods
147 patients with IPF (77% male, mean FVC 77.7% predicted) who were receiving a stable dose of antifibrotic therapy (AF) or not receiving AF (non-AF) were randomised and treated with BI 1015550 (AF n=49; non-AF n=48) or placebo (AF n=25; non-AF n=25) for 12 weeks. Total RNA was isolated from peripheral blood. The effect of BI 1015550 on gene expression profiles and their association with change from baseline in FVC were analysed based on background AF.

Results
There were no significant differences in gene expression profiles between treatment groups. However, in patients treated with BI 1015550 there were significant correlations between change in several fibrosis-linked genes and change in FVC over time in both the AF and non-AF groups; the most highly correlated genes differed between groups. These genes have not previously been linked to FVC change in IPF.

Conclusions
These data are consistent with PDE4B inhibition acting primarily on the lung, with little effect seen on circulating inflammatory cells in patients with IPF.