Comparison of Vedolizumab treatment to Adalimumab dose intensification in Crohn’s disease patients with loss of response or biomarker activity to Adalimumab on first line with therapeutic drug concentration: A randomized, multicentre, controlled VEDIAN trial.

INTERVENTION: Product Name: Entyvio 300 mg powder for concentrate for solution for infusion,Product Code: PRD1598541,Pharmaceutical Form: SOLUTION FOR INFUSION,Other descriptive name: ,Strength: Vedolizumab 60mg,Product Name: Humira 20 mg solution for injection in pre‐filled syringe,Product Code: PRD5952375,Pharmaceutical Form: SOLUTION FOR INJECTION,Other descriptive name: ,Strength: Adalimumab 20mg / 0.2mL CONDITION: Crohn's disease ; MedDRA version: 20.0Level: LLTClassification code: 10013099Term: Disease CrohnsSystem Organ Class: 10017947 MedDRA version: 20.0Level: LLTClassification code: 10013099Term: Disease CrohnsSystem Organ Class: 10017947 Therapeutic area: Diseases [C] ‐ Digestive System Diseases [C06] PRIMARY OUTCOME: Main Objective:To evaluate the efficacy, in terms of clinical and biomarker remission at 24 weeks, of a Vedolizumab treatment strategy compared to an Adalimumab (ADA) dose optimization treatment strategy in Crohn's disease patients with loss of secondary response and/or high biomarker activity on standard‐dose Adalimumab maintenance therapy with therapeutic drug levels. Primary end point(s):The primary objective will be to compare the proportion of clinical and biomarker remission (composite score) in the two groups of CD patients by 24 weeks after inclusion (ADA optimized versus Vedolizumab as second line). Secondary Objective:To evaluate the impact of a therapeutic strategy with Vedolizumab compared to a therapeutic strategy with Adalimumab (ADA) dose optimization on : Deep remission at W24 without treatment failure,To evaluate the impact of a therapeutic strategy with Vedolizumab compared to a therapeutic strategy with Adalimumab (ADA) dose optimization on : Treatment failure at W24 and W52,To evaluate the impact of a therapeutic strategy with Vedolizumab compared to a therapeutic strategy with Adalimumab (ADA) dose optimization on : Percentage of adverse events at W24 and W52,To evaluate the impact of a therapeutic strategy with Vedolizumab compared to a therapeutic strategy with Adalimumab (ADA) dose optimization on : Symptomatic remission at W24,To evaluate the impact of a therapeutic strategy with Vedolizumab compared to a therapeutic strategy with Adalimumab (ADA) dose optimization on : Evolution of IBDQ‐32 quality‐of‐life score at W24,To evaluate the impact of a therapeutic strategy with Vedolizumab compared to a therapeutic strategy with Adalimumab (ADA) dose optimization on : clinical and biomarker remission rates at W12 and W52,To analyze CDST score for prediction of clinical remission and biomarkers at W24 in each treatment arm. INCLUSION CRITERIA: Major patient and having given consent to participate in the study,Patients with Crohn's disease who have responded primarly to Adalimumab princeps or similar bio with loss of response to Adalimumab (40 mg every two weeks) with therapeutically adequate levels of ADA (> 7.5 µg/mL). SECONDARY OUTCOME: Secondary end point(s):Analyze the CDST (clinical decision support tool) score for prediction of remission under vedolizumab and adalimumab optimization. Secondary end point(s):Compare deep remission defined as clinical remission (clinical activity score < 150 with fecal calprotectin < 250 mcg/g stools and CRP < 5mg/L and either CDEIS <3 using ileocolonoscopy or Lewis score < 135 in the small bowel using VCE or no disease activity on MRE (defined by segmental Maria score < 7) or no bowel thickness on US according to the previous tools used at inclusion at W24. Secondary end point(s):Compare evolution of IBDQ‐32 in the two groups of patients between inclusion and W24 Secondary end point(s):Compare rates of clinical and biomarker remission at W12 Secondary end point(s):Compare rates of clinical and biomarker remission at W52 Secondary end point(s):Compare the percentage of adverse events in both arms at W52 Secondary end point(s):Compare treatment failure at W24 or W52 in the 2 groups Secondary end point(s):rate of Mucosal healing on imaging or endoscopy at W24 Secondary end point(s):Symptomatic remission at W24 is a composite criterion measured by PRO2 defined as: Stool frequency (SF) < 4 with abdominal pain score (AP) < 2 at W24; AND absence of therapeutic failure between inclusion and W24.