Clinical trial NCT03351647: Predictive Factors of Clinical Response to Ustekinumab in Active Crohn's Disease
Official title: Identification of Biological Predictive Factors of Clinical Response to Ustekinumab in Patients With Anti-Tumor Necrosis Factor (TNF) Antagonists Refractory Crohn's Disease: Interest of Dosage of C Reactive Protein (CRP), Calprotectin, Ustekinumab Through Levels and Antibodies
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Crohn Disease
Keywords: Crohn Disease
Ustekinumab
Vedolizumab
anti-TNF
CRP
calprotectin
cohort
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2017-11-24
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 18
Standard ages: ADULT
Accepts healthy volunteers: no
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.

Brief 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


Eligibility criteria: Inclusion Criteria:

* Age \> 18 years old
* Man or non pregnant woman
* Diagnostic attested of Crohn's disease
* Active Crohn's disease, with HBI score ≥ 4
* Previous treatment by at least one anti TNF and / or vedolizumab,, with primary non response, secondary loss of response or unacceptable side effects
* Formal indication of treatment by ustekinumab
* Patient informed and not opposed to his participation at the study

Exclusion Criteria:

* Pregnancy
* Evolutive cancer
* Evolutive and uncontrolled infection
* Psychiatric pathology that could interfere with the follow-up
* Refusal of the patient

Primary outcomes:
measure: Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 8.
timeFrame: Week 8
Secondary outcomes:
measure: Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 4.
timeFrame: Week 4
measure: Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 16.
timeFrame: Week 16
measure: Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 24.
timeFrame: Week 24
measure: Dosage in blood at week 4
timeFrame: Week 4
measure: Dosage in blood at week 8
timeFrame: Week 8
measure: Dosage in blood at week 16
timeFrame: Week 16
measure: Dosage in blood at week 24
timeFrame: Week 24
measure: Dosage of calprotectin in stools at week 4
timeFrame: Week 4
measure: Dosage of calprotectin in stools at week 8
timeFrame: Week 8
measure: Dosage of calprotectin in stools at week 16
timeFrame: Week 16
measure: Dosage of calprotectin in stools at week 24
timeFrame: Week 24
measure: Physical evaluation at week 4
timeFrame: Week 4
measure: Physical evaluation at week 8
timeFrame: Week 8
measure: Physical evaluation at week 16
timeFrame: Week 16
measure: Physical evaluation at week 24
timeFrame: Week 24
measure: Clinical evaluation at week 4
timeFrame: Week 4
measure: Clinical evaluation at week 8
timeFrame: Week 8
measure: Clinical evaluation at week 16
timeFrame: Week 16
measure: Clinical evaluation at week 24
timeFrame: Week 24
Other outcomes:
Locations:
city: Pierre-Bénite
country: France
facility: Centre hospitalier Lyon Sud
Study officials:
References: