Top-down Infliximab Study in Kids with Crohn's disease (TISKids): an international multicentre randomised controlled
M A Cozijnsen1, M van Pieterson1, J N Samsom2
1Department of Paediatric Gastroenterology , Erasmus University Medical Centre-Sophia Children's Hospital , Rotterdam , The Netherlands.
Insights
Early infliximab (IFX) treatment for pediatric Crohn's disease (CD) may improve outcomes. This study compares a top-down approach with IFX to a step-up strategy, assessing healing, complications, and surgery rates in new-onset CD patients.
Area of Science:
- Pediatric Gastroenterology
- Immunology
- Clinical Trials
Background:
- Crohn's disease (CD) is a chronic gastrointestinal inflammatory condition requiring lifelong management.
- Current treatment often involves a step-up strategy, reserving infliximab (IFX) for refractory cases.
- This approach can lead to severe complications and the need for surgery.
Purpose of the Study:
- To evaluate the efficacy of a top-down treatment strategy using IFX as first-line therapy in pediatric CD.
- To compare top-down versus step-up treatment regarding mucosal healing, disease activity, and complications.
- To assess long-term outcomes including surgery and hospitalization rates in newly diagnosed pediatric CD patients.
Main Methods:
- An international, multicenter, open-label, randomized controlled trial (NCT02517684).
- Recruitment of children (3-17 years) with new-onset, moderate-to-severe CD (wPCDAI > 40).
- Randomization to either top-down (IFX + azathioprine) or step-up (standard induction + azathioprine) treatment arms.
Main Results:
- Primary outcome: clinical remission (wPCDAI < 12.5) at 52 weeks without additional therapy or surgery.
- Secondary outcomes: mucosal healing, disease activity, growth, quality of life, and adverse events over 5 years.
- This is a pre-results abstract, actual findings are pending.
Conclusions:
- The top-down approach with early IFX administration is hypothesized to yield superior outcomes in pediatric CD.
- This strategy may reduce disease complications, surgical interventions, and hospitalizations.
- Further research is needed to confirm the long-term benefits of early IFX therapy.
Introduction:
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 And Analysis:
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.
Ethics And Dissemination:
Conducted according to the Declaration of Helsinki and Good Clinical Practice. Medical-ethical approval will be obtained for each site.
Trial Registration Number:
NCT02517684; Pre-results.
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