Infliximab Accelerated Induction for Moderate to Severe Ulcerative Colitis in Children (INDUCE) Trial

General intervention scheme:

The decision to start IFX is the sole decision of the treating physician based on the patient's immediate need. Eligible patients are those who are planned to start IFX. All patients will undergo clinical and laboratory evaluation for IFX eligibility (PPD, infectious serology). If the tests have already done in the last 3 months, we will use these data, there is no need to repeat. Patients must have a negative stool culture, stool for parasites and clostridium difficile toxin test performed over the last week in order to be eligible. The screening visit may be performed concomitantly with the enrolment visit if all inclusion and exclusion criteria are met.

Patients will be enrolled at the first screening visit. Informed consent will be signed by both parents is required during enrollment. Informed assent will be offered for patients 14 years old and older. Eligible patients, ambulatory UC patients, requiring IFX for corticosteroid dependent or refractory moderate to severe disease (excluding acute severe UC), meeting inclusion/exclusion criteria, after obtaining informed consent, will be randomized (1:1 ratio in blocks of four, stratified by immunomodulators use) at enrollment visit (week 0, prior to IFX initiation) to either group 1 or group 2 using opaque, numbered and sealed envelopes. Prior corticosteroid treatment is allowed as a taper-down schedule during induction with IFX and must be terminated by week 10 (otherwise will be defined as induction failure). At each visit all patients will be examined and have height, weight, and PUCAI performed as well as comprehensive laboratory examinations including CBC, albumin, AST, ALT, ESR and CRP (CRP will be measured and registered in mg/dL) and fecal samples (4 grams) for bile acids and microbiome/virome. Fecal sample for fecal calprotectin (FC) will be obtained as well at weeks 20 and 52. Extent of disease will be registered using the Paris classification (Levine A et al, IBD, June 2011) and will be based on the latest colonoscopic evaluation (described only by macroscopic involvement). Patients who undergo a colonoscopy at any time as standard of care before initiating biologic therapy should register the results of colonoscopy (according to the Mayo score- A score of ≤1 is considered complete mucosal healing). In addition, every colonoscopy that will be performed during the study period based on physician discretion, should be register in the CRF (Colonoscopy is not part of this specific protocol).

The study period is composed of two distinctive phases: Intervention phase: week 0-20 and follow-up phase: week 21-52.

Group 1 (intervention group): Patients in group 1 will receive an accelerated induction at 0,1,3 weeks (5 mg/kg) and then at week 7,11,15.