title: Top-down Infliximab Study in Kids with Crohn's disease (TISKids): an international multicentre randomised controlled trial.
abstract: BACKGROUND
  Crohn's disease (CD) is a chronic inflammatory disease predominantly affecting the gastrointestinal tract. CD usually requires lifelong medication and is accompanied by severe complications, such as fistulae and strictures, resulting in surgery. Infliximab (IFX) is very effective for treating paediatric patients with CD, but is currently only registered for therapy refractory patients-the so-called step-up strategy. We hypothesise that using IFX first-line, that is, top-down, will give more mucosal healing, fewer relapses, less complications, need for surgery and hospitalisation.
  
  
  METHODS
  This international multicentre open-label randomised controlled trial includes children, aged 3-17 years, with new-onset, untreated CD with moderate-to-severe disease activity (weighted Paediatric Crohn's Disease Activity Index (wPCDAI)>40). Eligible patients will be randomised to top-down or step-up treatment. Top-down treatment consists of 5 IFX infusions combined with azathioprine (AZA). After these 5 infusions, patients will continue AZA. Patients randomised to step-up will receive standard induction treatment, either oral prednisolone or exclusive enteral nutrition, combined with AZA as maintenance treatment. The primary outcome is clinical remission (wPCDAI<12.5) at 52 weeks without need for additional CD-related therapy or surgery. Total follow-up is 5 years. Secondary outcomes include clinical disease activity, mucosal healing by endoscopy (at week 10 and optionally week 52), faecal calprotectin, growth, quality of life, medication use and adverse events.
  
  
  BACKGROUND
  Conducted according to the Declaration of Helsinki and Good Clinical Practice. Medical-ethical approval will be obtained for each site.
  
  
  BACKGROUND
  NCT02517684; Pre-results.
authors.affiliation: Department of Paediatric Gastroenterology , Erasmus University Medical Centre-Sophia Children's Hospital , Rotterdam , The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: Cozijnsen
authors.affiliation: Department of Paediatric Gastroenterology , Erasmus University Medical Centre-Sophia Children's Hospital , Rotterdam , The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Pieterson
authors.affiliation: Laboratory of Paediatrics , Erasmus University Medical Centre-Sophia Children's Hospital , Rotterdam , The Netherlands.
authors.forename: J N
authors.initials: JN
authors.lastname: Samsom
authors.affiliation: Department of Paediatric Gastroenterology , Erasmus University Medical Centre-Sophia Children's Hospital , Rotterdam , The Netherlands.
authors.forename: J C
authors.initials: JC
authors.lastname: Escher
authors.affiliation: Department of Paediatric Gastroenterology , Erasmus University Medical Centre-Sophia Children's Hospital , Rotterdam , The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: de Ridder
keywords: COST-EFFECTIVENESS; CROHN'S DISEASE; INFLIXIMAB; PAEDIATRIC GASTROENTEROLOGY; STEROID-SPARING EFFICACY