Maarten Cozijnsen

25 Chapter 1 General introduction Outline of this thesis In Chapter 2 we describe the MINI index we developed and validated. This non-invasive index identifies children with endoscopic remission with high sensitivity and specificity. In Chapter 3 we describe the international multicenter randomized controlled trial (RCT) we set up to compare the efficacy and safety of top-down treatment (starting with IFX from diagnosis) with the conventional step-up treatment strategy in newly diagnosed pediatric CD patients. In a pilot analysis of the Infliximab Top-down Study in Kids with Crohn’s disease (ITSKids) multicenter randomized trial in Chapter 4, we demonstrate that IFX treatment has a strong effect on mRNA expression and protein concentrations by reducing Th1 and neutrophil signatures, and tissue remodeling proteins. In Chapter 5 we describe the real-world effectiveness of ADA treatment for children and adolescents with CD who had previously failed IFX treatment in a nationwide, observational cohort study. In Chapter 6 we review the benefits and risks of combining anti-TNF treatment with immunomodulator therapy based on published evidence.