Gene expression is associated with change in disease activity measured by DCE-MRI.

(A) High signature score correlates with Ktrans improvement in the treatment arm and Ktrans deterioration in the placebo arm. Scatter plots show baseline and treatment adjusted 14-week change in log Ktrans vs. signature score in both the treatment and placebo arms at weeks 2, 4, and 14. Linear models including terms for baseline Ktrans, treatment allocation, signature score, and the interaction between signature and treatment were fit to log Ktrans change from baseline at each week. At both week 4 and 14, the signature score main effect and interaction with treatment were significant at p<0.05. (B) Whole blood gene expression improves prediction of week 14 change in Ktrans. In ten repeated rounds of random subsampling, 40 patients were selected and their whole blood gene expression data was used to identify genes associated with treatment response measured by Ktrans, DAS28(CRP), and RAMRIS. A linear model including terms for baseline disease activity, treatment allocation, signature score, and the interaction between signature and treatment was fit to week 14 data and used to predict week 14 changes for held out subjects. The distribution of mean squared prediction errors (MSE) minus the MSE achieved by a model excluding signature score terms is plotted for each endpoint. For Ktrans, but not DAS28(CRP), or RAMRIS, incorporation of baseline blood gene expression consistently improved prediction performance (p = 0.015, t-test).