Towards personalized medicine in pediatric inflammatory bowel disease

In this thesis we aimed to contribute to the further development of personalized medicine in children and adolescents with inflammatory bowel disease (IBD). We focused on two different aspects: (1) the potential role of periodically measuring stool calprotectin levels, to see whether calprotectin can also be used to monitor response to treatment; and (2) profiling patients with pediatric-onset primary sclerosing cholangitis (PSC), a rare but severe hepatobiliairy disease that is strongly associated with IBD.
Using periodically measured stool calprotectin levels to monitor response-to-treatment is a relatively new application of this diagnostic test. In patients receiving remission-induction therapy, a shift of calprotectin concentrations into the target range appears to be a good surrogate marker for mucosal healing. Reaching the target calprotectin range within 3 months after starting the treatment predicts a favourable disease course in children with Crohn’s disease. Vice versa, patients who fail to reach target calprotectin levels within 3 months after conventional induction therapy may be entitled to step-up to a more aggressive treatment.
Until recently, childhood-onset PSC was believed to present with milder disease and a more favourable outcome than adult-onset PSC. By evaluating time-to-complication in children with PSC up until adulthood, we showed that paediatric- and adult-onset PSC run a similar progressive disease course. Furthermore, examination of the genetic material (DNA) of children with PSC and their biological parents revealed multiple rare candidate disease-causing variants.