Predictive Factors of Clinical Response to Ustekinumab in Active Crohn's Disease

NCT03351647 | Completed

• 1 other identifier: 69HCL17_0218
• Study Type: observational
• Target: 18
• Locations: 1 country
• Sites: 1

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

Conditions

Crohn Disease

Keywords

Crohn Disease; Ustekinumab; Vedolizumab; anti-TNF; CRP; calprotectin; cohort

Outcome Measures

Primary Outcomes (1)

• Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 8.

  Dosage of ustekinumab through level and ustekinumab antibodies: one 4ml blood sample

  Week 8

Secondary Outcomes (19)

• Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 4.

  Week 4

• Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 16.

  Week 16

• Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 24.

  Week 24

• Dosage in blood at week 4

  Week 4

• Dosage in blood at week 8

  Week 8

Study Arms (1)

Group Ustekinumab

Patients presenting an active crohn's disease (HBI score ≥ 4) with an indication of treatment by ustekinumab because of failure or unacceptable side effects of previous treatments, and who have already been treated by at least one anti TNF The patients must be 18 years old or older.

Biological: Evaluation of biological predictive factors of clinical response to ustekinumab

Interventions

Evaluation of biological predictive factors of clinical response to ustekinumab BIOLOGICAL

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.

Group Ustekinumab

Eligibility Criteria

• Age: 18 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• 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.

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Centre hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Three blood samples of 4 ml, one stool sample of 50 mg

MeSH Terms

Conditions

Crohn Disease

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2017
• First Posted: November 24, 2017
• Study Start: February 14, 2018
• Primary Completion: August 29, 2018
• Study Completion: September 23, 2019
• Last Updated: August 24, 2022

Record last verified: 2022-08

Locations

FR (1)