Predictive Factors of Clinical Response to Ustekinumab in Active Crohn's Disease
Condition: Crohn Disease
MeSH terms: Crohn Disease
Study type: Observational

Summary: 
      Ustekinumab is a fully human Immune Globulin Gk (IgGk) monoclonal antibody against the common
      p40 subunit of interleukin-12 and interleukin-23, which are implicated in the pathogenesis of
      inflammatory bowel disease. Its efficiency to induce and maintain clinical response in
      patients with anti TNF resistant Crohn's disease has been proved in several clinical trials,
      and the profile of safety of this treatment was good, but the investigators have few data
      about biological characteristics of patients treated by Ustekinumab, particularly about
      ustekinumab through levels and rate of patients developing anti ustekinumab antibodies during
      the induction and maintenance stages, and no predictive factors of clinical response have
      been identified yet.

      The aim of this study will be to assess the evolution of biological markers of inflammation
      and ustekinumab trough levels and antibodies, in responders and non responders patients
      treated by ustekinumab, in order to identify predictive factors of clinical response.

      The investigators will perform a prospective observational study, including the patients
      followed in the University hospital center of Lyon and treated by ustekinumab for a moderate
      to severe Crohn's disease (with a HBI score≥4 ). All the patients included will have been
      previously treated by at least one anti TNF and/or Vedolizumab, with specified criteria for a
      primary non response, a secondary loss of response or unacceptable side effects.

      Then, clinical and biological data will be collected for each patient at the inclusion, and
      then at weeks 4, 8, 16, 24: HBI score, sides effects, extra intestinal manifestations,
      steroids withdraw, CRP, calprotectin, ustekinumab trough levels and ustekinumab antibodies.

      The investigators will compare responding and non responding patients at week 16 (end of the
      induction period) according to these data.

      The hypothesis the investigators state is that an early and significant decrease of the
      inflammation markers in blood and stools associated with a high ustekinumab through level in
      blood is associated with a clinical response at week 16 in the patients treated by
      ustekinumab
    


Intervention name(s): Evaluation of biological predictive factors of clinical response to ustekinumab
Intervention type(s): Biological
Intervention description(s): The clinical response is defined as a decrease in the Crohn's Disease Activity Index (CDAI) score ≥ 100 points or a decrease in the HBI score ≥ 3 points.
Intervention MeSH terms: Ustekinumab
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        This study is conducted in adults with moderate to severe active Crohn's disease who are
        resistant to TNF and Vedolizumab.
      
Biospecimen description: 
      Three blood samples of 4 ml, one stool sample of 50 mg
    
Keywords: Crohn Disease; Ustekinumab; Vedolizumab; anti-TNF; CRP; calprotectin; cohort