RECRUITINGPhase 4INTERVENTIONAL

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.

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 Trial

About This Trial

A substantial fraction of IBD patients with an initial response to infliximab or adalimumab later experience re-emerging active disease despite ongoing anti-Tumour Necrosis Factor (TNF) agents maintenance therapy. The optimal intervention in patients with secondary loss-of-response (LOR) is still poorly defined, as there are still scant data on how best to choose the next intervention from among dose-intensification, switch to another anti-TNF or switch out of the anti-TNF class. Moreover, according to STRIDE 2 recommendations and CALM study, optimize patients based solely on lack of biological remission (CRP, calprotectin) can be discuss. If CALM study has showed that the intervention arm based on regular monitoring fecal calprotectin, CRP and/or CDAI to optimize patients under adalimumab was significantly associated to an increase rate of mucosal healing that the standard of care strategy based on only clinical activity, TDM was not available to guide drug optimization strategy.

Who May Be Eligible (Plain English)

Who May Qualify: - Major patient and having given consent to participate in the study - Patients with Crohn's disease who have responded primary 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). - Patient affiliated to or entitled under a social security scheme Who Should NOT Join This Trial: - Pregnant woman - Patient unable to perform MRI or VCE or ileocolonoscopy or ultrasound less than one month before inclusion - Previous or current use of vedolizumab or ustekinumab for Crohn's disease or participation in a biological study - Concomitant use of immunomodulators - Patients on corticosteroid therapy - History of cancer - History of human weakened immune system virus (HIV), weakened immune system syndrome, central nervous system (CNS) demyelinating disease (including myelitis), neurological symptoms suggestive of demyelinating disease, chronic recurrent infection, active tuberculosis (received or untreated), severe infections such as sepsis and opportunistic infections - Patient with ileoanal pouchitis or ileorectal anastomosis - Patient with short small bowel syndrome as determined by investigator - Patients receiving total parenteral nutrition (TPN) - Patients receiving enteral nutrition - Patient under legal protection or unable to give consent - Hemorrhagic rectocolitis or indeterminate colitis - Patients treated with concomitant immunosuppressive agents - Patient treated with an optimized dose of adalimumab - Primary non-responder to Adalimumab - Patient previously treated with infliximab or ustekinumab before adalimumab - Severe relapse defined by CDAI \> 330 - Patient with anoperineal Crohn's disease - Crohn's disease patient with transient or permanent stoma. Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * Major patient and having given consent to participate in the study * Patients with Crohn's disease who have responded primary 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). * Patient affiliated to or entitled under a social security scheme Exclusion Criteria: * Pregnant woman * Patient unable to perform MRI or VCE or ileocolonoscopy or ultrasound less than one month before inclusion * Previous or current use of vedolizumab or ustekinumab for Crohn's disease or participation in a biological study * Concomitant use of immunomodulators * Patients on corticosteroid therapy * History of cancer * History of human immunodeficiency virus (HIV), immunodeficiency syndrome, central nervous system (CNS) demyelinating disease (including myelitis), neurological symptoms suggestive of demyelinating disease, chronic recurrent infection, active tuberculosis (received or untreated), severe infections such as sepsis and opportunistic infections * Patient with ileoanal pouchitis or ileorectal anastomosis * Patient with short small bowel syndrome as determined by investigator * Patients receiving total parenteral nutrition (TPN) * Patients receiving enteral nutrition * Patient under legal protection or unable to give consent * Hemorrhagic rectocolitis or indeterminate colitis * Patients treated with concomitant immunosuppressive agents * Patient treated with an optimized dose of adalimumab * Primary non-responder to Adalimumab * Patient previously treated with infliximab or ustekinumab before adalimumab * Severe relapse defined by CDAI \> 330 * Patient with anoperineal Crohn's disease * Crohn's disease patient with transient or permanent stoma.

Treatments Being Tested

DRUG

Adalimumab

Administration of adalimumab with optimisation either 80 mg every 14 days by subcutaneous injection, or the same dose of 40 mg every 7 days.

DRUG

Vedolizumab

Strategy B: administration of vedolizumab 300mg by infusion at baseline, 14 days, 42 days and 60 days, followed by a dose of 108mg every fortnight by subcutaneous injection.

Locations (12)

APHP - Hôpital Bicêtre

Le Kremlin-Bicêtre, Paris, France

CHU Amiens

Amiens, France

CHRU Lille

Lille, France

Chu Limoges

Limoges, France

APHM

Marseille, France

CHU Montpellier

Montpellier, France

Hôpital de l'Archet II

Nice, France

Assistance Publique - Hôpitaux de Paris

Paris, France

CHU Bordeaux

Pessac, France

Ch Lyon Sud

Pierre-Bénite, France

CHU Rennes

Rennes, France

CHU de Saint-Etienne

Saint-Etienne, France