Maarten Cozijnsen

75 Chapter 4 Infliximab impacts leukocyte RNA expression and serum inflammatory proteins external controls (in triplicate) are included in the assay. The manufacturer of the protein assay, Olink Bioscience (Uppsala, Sweden), had no input on the study design, analysis or manuscript preparation. The data was analyzed pairwise with the Wilcoxon signed-rank test in SPSS version 21 (IBM SPSS Statistics, Armonk, NY, USA). FDR correction was then performed in R (version 3.3.2) using the Benjamini-Hochberg procedure, using an FDR of 0.1 as threshold of significance. General statistical analyses and ethical statement Clinical data were analyzed using SPSS version 21 (IBM SPSS Statistics, Armonk, NY, USA). Continuous non-parametric data are presented as median (range) and categorical data by number (percentage). We used the Mann Whitney U Test and Fisher Exact Test where appropriate to compare between treatment groups and the Wilcoxon signed-rank test to compare paired samples within a treatment group, using α 0.01 as threshold for significance. We used Pearson’s correlation coefficient to measure the association of RNA expression and proteins concentrations with the degree of endoscopic disease activity (SESCD). Missing data were left out of the analyses. Data was visualized using GraphPad Prism version 5.01. The heatmap was composed in OmniViz version 6.0.1 (BioWisdom Ltd., Cambridge, United Kingdom): for each probe set, the geometric mean of the hybridization intensity was calculated, and level of expression was visualized relative to the geometric mean. This study was carried out in three centers: The Erasmus Medical Centre in Rotterdam and Maasstad Hospital in Rotterdam, the Netherlands, and in the Sapienza University Hospital in Rome, Italy. Medical ethical approval was obtained in each country and for each site and written informed consent was obtained from each patient before randomization.