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.

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.

To compare the proportion of deep remissions, the composite score is :

• Clinical and biomarker remission at week 24 ;
• AND Mucosal remission at week 24;
• AND no treatment failure between inclusion and week 24.

A patient is considered to be in clinical remission if they present:

• A Crohn's Disease Activity Index (CDAI score) < 150 at week 24 ;
• OR a CDAI score ≥ 150 at week 24 AND a CDAI score < 150 at inclusion AND an increase < 70 points between inclusion and week 24.

CDAI is the Crohn's disease activity score most commonly used in clinical trials. A CDAI below 150 corresponds to inactive Crohn's disease; between 150 and 450 to active Crohn's disease; above 450 to severe Crohn's disease.

Biomarkers are considered to be standardised if the following are observed

• normalisation of faecal calprotectin: faecal calprotectin < 250 µg/g at week 24.

Biomarkers are considered to be standardised if the following are observed

• Normalisation of serum C-reactive protein (CRP) : serum CRP < 5 mg/L at week 24 ;

A patient is considered to be in endoscopic remission if they have:

• a CDEIS score < 3 at week 24 using ileocolonoscopy ; The CDEIS is an index of the severity of intestinal lesions caused by Crohn's disease.

The CDEIS ranges from 0 to 44 0: no lesions 44: most severe lesions Endoscopic remission defined by a CDEIS ≤ 7

A patient is considered to be in endoscopic remission if they have:

• a Lewis score < 135 at week 24 in the small bowel using VCE (video endoscopy); The Lewis score analyses 5 mucosal parameters for each of the four segments of the small bowel (duodenum, jejunum, proximal and distal ileum): erythema, oedema, presence of nodular lesions, ulcerations and stenosis. A Lewis score < 135 indicates inactive disease.

A patient is considered to be in endoscopic remission if they have:

• no ulceration using endoscopic video capsule (VCE) at week 24;

A patient is considered to be in endoscopic remission if they have:

• no activity on MRI at week 24 (defined as segmental MaRIA score < 7); The MaRIA (Magnetic Resonance Index of Activity) scoring system is used to assess ileocolic Crohn's disease activity on contrast-enhanced MRI enterography. The segmental index represents the severity of disease in a segment of the bowel, while assessing six defined anatomical regions that can be combined to form an overall MaRIA index.

The cut-off points for the MaRIA score are as follows:

moderate disease: ≥7 severe disease: ≥11

A patient is considered to be in endoscopic remission if they have:

• no bowel thickness on ultrasound at week 24 (< 3mm with no other signs of activity).

Compare treatment failure at week 24 or week 52 in the 2 groups.

Treatment failure is defined as:

• The performance of a CD-related surgery between inclusion and week 24 ;
• OR use of steroids between baseline and week 24;
• OR treatment dose optimisation between inclusion and week 24;
• OR a change in treatment between inclusion and week 24.

Compare the percentage of adverse events in both arms at week 52

Symptomatic remission at week 24 is a composite criterion measured by PRO2 defined as: Stool frequency (SF) < 3 with abdominal pain score (AP) < 2 at week 24; AND absence of therapeutic failure between inclusion and week 24.

Compare evolution of IBDQ-32 in the two groups of patients between inclusion and week 24.

The IBDQ-32 questionnaire consists of 32 questions. Each question is answered on a scale from 1 to 7, with 1 being the lowest score and 7 the highest. Adding up the different scores gives a total score, ranging from 32 (worst score) to 224 (best score). The higher the score, the better the quality of life.

Compare rates of clinical and biomarker remission at week 12 and week 52.

Rate of Mucosal remission at week 24. Mucosal remission is definied by ;

• a CDEIS score < 3 at week 24 using ileocolonoscopy ; The CDEIS is an index of the severity of intestinal lesions caused by Crohn's disease.
• Or a Lewis score < 135 at week 24 in the small bowel using VCE (video endoscopy)
• Or no ulceration using endoscopic video capsule (VCE) at week 24;
• Or no activity on MRI at week 24 (defined as segmental MaRIA score < 7);
• Or no bowel thickness on ultrasound at week 24 (< 3mm with no other signs of activity).

Analyze the CDST score for prediction of remission under vedolizumab and adalimumab optimization.

A CDST score :

• < 13 points is considered a low probability of remission;
• Between 13 and 19 points is considered an intermediate probability of remission;
• > 19 points is considered a high probability of remission.

Compare the efficacy of each strategy based on baseline serum ADA levels, classified into three groups: Pharmacodynamic failure: Therapeutic level of ADA in blood (> 7.5 µg/mL) Pharmacokinetic failure: Subtherapeutic level of ADA in blood (< 7.5 µg/mL) Immunogenic failure (undetectable serum ADA level with the presence of anti-ADA antibodies >50 ng/mL).