EFFICACI : EFFicacy of Intravenous Infliximab Versus Vedolizumab After Failure of subCutaneous Anti-TNF in Patients With UlCerative Colitis

Design :

A prospective, multicenter, randomized, double blind clinical trial

Primary objective :

To determine whether a non-TNF-targeted biologic (vedolizumab) is superior to infliximab to treat patient with UC losing response or with a primary failure to a first subcutaneous anti-TNF drug at week 14.

Secondary objective :

• To assess the rate of clinical response and remission at Week 54 in each group of treatments and the time to clinical response and remission from baseline ;
• To assess the changes in faecal calprotectin levels from baseline to week 14 and 54 according to treatment ;
• To assess the rate of colectomy and hospitalization in each treatment group ;
• To assess the rate of mucosal healing at week 14 and 54 in each group of treatments ;
• To assess the rate of loss of response in each group of treatments for patients responder after induction phase ;
• To assess the changes of quality of life indexes and the disability index from baseline to week 14 and 54 ;
• To determine the safety profile of each group of treatments ;
• To characterize the response in each group of treatments according to drug monitoring of the first anti-TNF agent ;
• To describe the pharmacokinetics of infliximab and vedolizumab as second-line treatment of UC and explore the sources of pharmacokinetic inter-individual variability ;
• To identify predictive factors of response to the treatment, including pharmacokinetic features

Expected findings and impact:

The patients include in the clinical will not lose any benefit since both treatments are actually indicated and effective in this condition. In both arm of treatment, patients will receive an effective treatment.

The study will optimize physician decision making to decrease the disease activity period in UC patients with known consequence such as hospitalisation, surgery, work cessations with related cost effects.

Inclusion criteria

• Male or non-pregnant female, non-lactating female;
• 18 years of age or older and less than 75 years ;
• Documented diagnosis of UC for at least 6 months ;
• Left side colitis or pancolitis ;
• Moderate to severe disease according to a Mayo score equal or above 6 with a Mayo endoscopic sub-score of 2 or 3 ;
• Active disease despite ongoing treatment with adalimumab or golimumab for at least 12 weeks (inadequate response, failure, loss of response or intolerance) ;
• Ability of the subject to participate fully in all aspects of this clinical trial ;
• Written informed consent must be obtained and documented ;
• Naïve to Janus kinase inhibitor (JAK inhibitor) ;
• Affiliation to the national health insurance.

Non inclusion Criteria:

• Contraindication to continue TNF antagonist (ongoing abscess(es), clinical suspicion of tuberculosis, past allergic reaction) ;
• Contraindication to vedolizumab treatment ;
• Steroid treatment > 20 mg/day for at least two weeks before baseline ;
• Proctitis ;
• Stoma ;
• Proctocolectomy or subtotal colectomy ;
• Planned surgery within the year of the trial ;
• Previous exposure to vedolizumab or infliximab ;
• History of cancer during the past 5 years ;
• Pregnancy or breastfeeding
• Adults legally protected (under judicial protection, guardianship, or supervision), persons deprived of their liberty.
• Ongoing participation to another interventional study