Journey to improve pediatric Crohn’s disease treatment

The aim of this thesis was to compare the efficacy and safety of the experimental top-down treatment strategy with the conventional step-up treatment strategy in children and adolescents with Crohn’s disease (CD). In the top down strategy, patients start with infliximab – a highly effective treatment option – instead of reserving it for those that don’t respond to other treatment options (e.g. prednisolone, exclusive enteral nutrition, azathioprine), which is the conventional step-up strategy. The study is still ongoing. Chapter 3 describes the study protocol and Chapter 4 describes the results of an analyses of the immune responses of patients treated in a trial with a similar design. It demonstrates that infliximab treatment reduces systemic and intestinal CD inflammation more effectively than prednisolone treatment does. Chapter 2 describes the accuracy of a novel mucosal inflammation, non-invasive (MINI) index that strongly correlates with mucosal inflammation and that can accurately assess endoscopic remission. The MINI index can be used both in clinical practice for tight monitoring of mucosal inflammation and facilitating appropriate selection of children for ileocolonoscopy, and serve as an outcome measure in clinical trials instead of, or in addition to ileocolonoscopy to increase feasibility and enrollment rates. The last two chapters describe the results of a nationwide, observational case series which assessed the safety and effectiveness of adalimumab therapy in pediatric CD patients that previously failed infliximab treatment (chapter 5) and a review of scientific literature that compares the benefits and risks of combining anti-TNF treatment with immunomodulator therapy based on published evidence.

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