Evaluation of the Clinical and Immunological Impact of Two Therapeutic Strategies in Chronic Inflammatory Diseases

Study Overview
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Brief Summary
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This study evaluates 2 therapeutic strategies (increase infliximab dose or add an immunosuppressant) in patients with inflammatory bowel disease in loss of response to infliximab. Addition of an immunosuppressant may be more efficient at long term and is less expensive.

Official Title
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Evaluation of the Clinical and Immunological Impact of Two Therapeutic Strategies (Increasing the Infliximab Dose or Introduction of Immunosuppressive Therapy) in Patients Chronic Inflammatory Bowel Diseases in Loss of Response to Infliximab

Conditions
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Inflammatory Bowel Diseases

Intervention / Treatment
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* Drug: Infliximab
* Drug: Mercaptopurine
* Drug: Azathioprine
* Drug: Infliximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with ulcerative colitis or crohn's disease treated with infliximab (5mg/kg per 8 weeks) and with loss of response after at least 4 infusions of infliximab active disease ( HBI > 5 for CD patients or SCCAI> 6 for UC patients) patients treated with infliximab only at the time of loss of response Exclusion Criteria: Patients with CD with ano perineal lesions and without luminal activity patients treated with cortico steroids and having had history of intolerance to azathioprin, 6-mercaptopurine or methotrexate patients with acute severe flare (HBI>12 for CD patients and Lichtiger score > 10 for UC patients) pregnant female patients with anal disease alone

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Optimisation strategy<br>increase of Infliximab dose from 5mg/kg every 8 weeks to Infliximab 10 mg/kg every 8 weeks | Drug: Infliximab<br>* Infliximab 10mg/kg every 8 weeks<br>|
| Other: Addition strategy<br>same dose of Infliximab ( 5mg/kg every 8 weeks) with addition of immunosuppressive agent: Azathioprine or Mercaptopurine | Drug: Mercaptopurine<br>* 6-mercaptopurine 1 à 1,5 mg/kg<br>* Other names: addition strategy with 6-mercaptopurine in second intention;Drug: Azathioprine<br>* Azathioprine 2 à 2.5mg/kg/j<br>* Other names: addition strategy with azathioprine in first intention;Drug: Infliximab<br>* Infliximab 5mg/kg every 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients in Clinical remission | the clinical remission is defined by Harvey Bradshaw (HBI) Index < 4 for Crohn's disease or Simple Clinical Colitis Activity Index (SCCAI)<4 for ulcerative colitis. | At Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients in deep remission | clinical remission associated with endoscopic remission (CDEIS <3 for CD patients or Mayo score<2 for UC patients) | At Week 52 | 
| Number of patient in remission and clinical response | clinical response is defined as a decrease of at least 3 points of HBI for CD patients or SCCAI for UC patients compared to baseline (week 0). Simple Clinical Colitis Activity Index (SCCAI)<4 for ulcerative colitisHBI pour MC et SCCAI pour RCH <4 associated at CRP < 5 mg/dl. | At week 16 | 
| infliximab blood concentration |  | Baseline, week 16 ad week 52 | 
| infliximab antibodies concentration |  | Baseline, week 16 ad week 52 | 
| economic criteria | medical fees in each arm | At week 52 | 
| number of patient with adverse effects and allergic reactions with infliximab |  | At week 52 | 
| Inflammatory bowel disease questionnaire (score IBDQ) | quality of life | Baseline and week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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crohn's disease, ulcerative colitis, infliximab, loss of response