Evaluation of Molecular Mechanisms of Non-response to Therapy in Patients With Inflammatory Bowel Disease

Inflammatory bowel diseases (IBD) represent a group of immune-mediated disorders, in which currently unidentified trigger factors drive the manifestation of chronic relapsing- remitting destructive inflammatory episodes in the gut. IBD comprise two main disease entities, ulcerati\\ie colitis (UC) and Crohn s disease (CD). The diseases differ in anatomical distribution, with continuous, uniform inflammation restricted to the colon in UC, and multifocal inflammation extended throughout the entire gastrointestinal tract from mouth to anus in CD. Clinical symptoms of IBD may include bloody stools, abdominal pain, fatigue, diarrhoea, fever and weight loss. Extra-intestinal symptoms occurring in up to 40% of patients, e.g. anaemia, skin lesions (e.g. erythema nodosum, pyoderma), arthritis and uveitis, and other complications directly related to the disease organ, such as fistula in CD are considered to reflect an overwhelming systemic inflammatory state. Disease onset typically manifests at age 15-35 years, men and women are almost equally affected. In addition, paediatric forms of IBD that often represent complex, se\\/ere monogenic forms of the disease, are seen. The incidence rates of IBD in Europe are about 6.3 (CD) and 11.8 (UC) per 100.000 persons. With growing incidence rates and overall reduced mortality the lifetime prevalence of IBD is expected to rise. The estimated lifetime prevalence of 0.3%-0.5% of the European population corresponds to estimates of 1.5-2 million patients with IBD.

Appropriate selection of therapies and their timing of introduction (decision support) in the course of IBD will be essential to reach a higher degree of disease control (across patients and within individual patients) than it is achie\\led today. In many instances, comparati\\ie data is missing and combinations or sequential therapies are not developed. In summary, despite some treatment successes, major challenges remain.

The investigators have decided to include patients with inflammatory bowel disease (IBD) in which targeted therapies are administered as part of standard helathcare and which aims at identifiyng solid biomarker signatures as well as molecular pathways and mechanisms linked to response and non-response to therapy. Choice od medications (which are all approved for first line use) is by treating physicians. All follow-up procedures are according to standards of care.


Eligibility Criteria:
Inclusion Criteria:

* Male and female patients ≥ 18 years of age (at the time of signing the Informed Consent)
* Person informed about study organization and having signed the informed consent.
* Established diagnosis of Crohn's dsease or ulcerative colitis with a minimum disease duration of 3 months
* Moderate to severe disease activity

  * UC : Mayo Score ≥ 6 including endoscopy score of ≥ 2
  * CD : CDAI score betwenn 220 and 450 (inclusive)
* Indication to start any biological or small molecule agent (anti-TNF, anti-IL 21/23, anti-integrin and JAK-inhibitors)
* In case of treatment with corticosteroid : stable dose for at least 3 weeks prior to baseline, dosage ≤ 20 mg prednisone
* Indication for colonoscopy for the assessment of disease activity as for standards of care and current guidelines
* Person affiliated to or beneficiary of a social security plan

Exclusion Criteria:

* Diagnosis of indeterminate colitis, microscopic colitis, ischaemic colitis, infectious colitis, radiation colitis
* Absolute contraindications to colonoscopy procedures, complication during previous endoscopy
* Bleeding disorders
* Indication for surgery for UC
* Rectal topical therapy (enemas or suppositories) ≤ 2 weeks prior to baseline
* Treatment with \> 20 mg prednisone within 3 weeks prior to baseline
* Anaemia (haemoglobbin \< 10g/dl) at baseline
* Subject unable to comply with the study procedures
* Person referred in articles L.1121-5, L. 1121-7 and L.1121-8 of the Public Health Code:

  * Pregnant, parturient or breastfeeding woman
  * Minor person (non-emancipated)
  * Adult person under legal protection (any form of public guardianship)
  * Adult person incapable of giving consent and not under legal protection
* Person deprived of liberty for judicial or administrative decision, person under psychiatric care as referred in articles L. 3212-1 and L. 3213-1.