Top Down Versus Step up in Pediatric Ulcerative Colitis

Study Overview
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Brief Summary
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Pediatric Ulcerative Colitis (UC) patients with moderate to severe disease activity at high risk of colectomy. Early use of biologic agents will likely be more effective. But there were no studies identified that compared a strategy of upfront biologic-based therapy versus gradual step-up therapy. In our study, newly diagnosed moderate to severe pediatric UC patients (6-18 years old) will be randomly divided into infliximab (IFX) treatment group (Top down group, TD) and corticosteroids (CS) treatment group (Step-up group, SU). Mucosal healing rate at week 12 will be compared between the two groups. The relapse rates and sustained durations of remission within one year will also be evaluated.

Detailed Description
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Pediatric ulcerative colitis (UC) is typically more extensive and has a more active disease course than adult UC. Pediatric UC patients with moderate to severe disease activity at high risk of colectomy. Rapid disease control may improve the prognosis of the disease and reduce the rate of surgery. Early use of biologic agents will likely be more effective. But there were no studies identified that compared a strategy of upfront biologic-based therapy versus gradual step-up therapy. In our study, newly diagnosed moderate to severe pediatric UC patients (6-18 years old) will be randomly divided into infliximab (IFX) treatment group (Top down group, TD) and corticosteroids (CS) treatment group (Step-up group, SU). A decrease of pediatric ulcerative colitis activity index (PUCAI) at least 20 points were defined as Clinical response. Clinical response will be evaluated at week 2 in SU group and week 6 in TD group. For no-responder, treatment plan will be changed. Clinical remission rate at week 10 and mucosal healing rate at week 12 will be compared between the two groups. The relapse rates and sustained durations of remission within one year will also be evaluated.

Official Title
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First-line Treatment With Infliximab Versus Corticosteroids in Children With Newly Diagnosed Moderate to Severe Ulcerative Colitis

Conditions
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Ulcerative Colitis, Infliximab, Children

Intervention / Treatment
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* Drug: Infliximab
* Drug: Corticosteroids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: newly diagnosed UC; moderate to severe disease activity Age: 6 to 18 years old Exclusion Criteria: with mild disease activity Have been treated with Corticosteroid or biological agents for UC

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Infliximab treatment group<br>For newly diagnosed moderate to severe Pediatric ulcerative colitis, infliximab will be used as first-line treatment | Drug: Infliximab<br>* Infliximab will be administered intravenously at a dose of 5 mg/kg for 0, 2, and 6 weeks, then every 8 weeks for 1 year.<br>* Other names: 5-ASA, AZA;|
| Active Comparator: Corticosteroid treatment group<br>For newly diagnosed moderate to severe Pediatric ulcerative colitis, corticosteroids will be used as first-line treatment | Drug: Corticosteroids<br>* Corticosteroid will be given at a dose of 1-2mg/kg/day (maximum 60 mg/kg/day),oral or intravenously for 12 to 14 weeks.<br>* Other names: 5-ASA, AZA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mucosal healing rate | The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) ≦1 points is defined as mucosal healing. This will be evaluated by inflammatory bowel disease endoscopist. | 12 week after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The relapse rates | Relapse is defined as an increased in pediatric Ulcerative Colitis activity index (PUCAI) score by 10 points or more after clinical remission or when new Ulcerative Colitis treatment needed to be started due to worsening of symptoms. This will be evaluated by gastroenterologist. | 1 year after intervention | 
| Sustained durations of remission | Sustained pediatric Ulcerative Colitis activity index (PUCAI) score <10 points during follow-up（week 10 to week 54 after intervention). This will be evaluated by gastroenterologist. | 1 year after intervention |