Clinical trial NCT05992142: ChAracterizing the Remission Status in Patients With Ulcerative Colitis Treated by 5-ASA
Official title: ChAracterizing the Remission Status in Patients With Ulcerative Colitis Treated by 5-ASA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Ulcerative Colitis
Keywords: remission
5-aminosalicylate acid (5-ASA)
Lead sponsor: Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW
Sponsor class: OTHER
Collaborators: name: Ferring Pharmaceuticals
First posted: 2023-08-15
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: transversal study
Primary purpose: TREATMENT

Brief summary: For the last years the aim of the management of ulcerative colitis (UC) has become more ambitious including not only clinical remission but also the achievement of biological remission, endoscopic and histological healing, which are associated with less flares, hospitalizations and surgeries. About 50% of the patients with UC followed in routine are treated by 5-aminosalicylate acid (5-ASA) (oral and/or topical). The aim of the study is to describe the different levels of remission (clinical, endoscopic, histological) in UC patients treated only by 5-ASA, that report to be in clinical remission during a routine follow-up visit. The factors associated with different levels of remission (demographic, 5-ASA regimen, biologic, endoscopic, histologic) will be studied. Adherence and quality of life will be examined through patient questionnaires.

Detailed description: The management of inflammatory bowel diseases aims to induce not only a clinical corticosteroid-free remission but also a deep remission defined by the achievement of mucosal healing. In ulcerative colitis (UC), mucosal healing has been nicely correlated with a better outcome of the disease. A lack of mucosal healing after a first steroid course is associated with a bad outcome including higher hospitalizations and more clinical relapses after 1 year. The absence of mucosal healing has also been correlated with higher rates of colectomy. Mucosal healing is defined by the absence of ulcers and includes patients with an endoscopic Mayo subscore of zero and one. Recently, a significantly better outcome has been demonstrated in patients having an endoscopic Mayo subscore of zero instead of one as well as a histological healing on the biopsies. The fecal biomarkers, especially the fecal calprotectin, have a high accuracy for the prediction of ongoing endoscopic and histologic inflammation in patients in clinical remission. Fecal calprotectin is well correlated with the Mayo endoscopic subscore and can discriminate patients with an endoscopic Mayo subscore of zero versus one or more by using a cut-off of 150 microgram/gram. A residual histologic inflammation is associated with a fecal calprotectin of 155 microgram/gram or more. Subsequently the management of UC has evolved and aims to induce a tighter control of the disease including a complete endoscopic response and a histological healing. It is currently not known how well these patients who report being in clinical remission are actually in objectively defined remission. As a deep remission is so important for the future evaluation of the disease, it is important to understand the factors linked to the absence of such remission.

The primary objective of this study is to describe the percentage of the different levels of remission (clinical, endoscopic, histological), in UC patients, treated by 5-ASA for at least 6 months, free of concomitant UC medications for at least 3 months and presenting for a routine follow-up visit.

The secondary objectives of this study are:

* to identify the factors associated to the absence of deep remission (demographic, UC history, clinical, biological, endoscopic, histological, 5-ASA regimen, adherence)
* to describe the adherence of the patients to the 5-ASA medications and its impact on the remission status.
* to describe the regimen of 5-ASA prescription (dosage, oral/local form) and its impact on the remission status.
* to describe the quality of life of the patients with UC on 5-ASA and its correlation with the level of remission.
* to understand the implication of patient's perspective and physician's perspective in patient lacking deep remission.
* to analyze the reasons of non-deep remission

This study is a national, multicenter, transversal, interventional study conducted in Belgium (16 centers will participate). The trial design is as follows:

* All subjects will undergo screening procedures. The screening visit of eligible patients will include the review of inclusion and exclusion criteria, and the informed consent form procedure. After screening, if the patient fulfils all inclusion and none of the exclusion criteria, and is willing to participate, the inclusion visit will be performed at the same time. The gastroenterologist will record the characteristics of patients and of the disease, medical history, current and past UC treatments in the last year before inclusion, and the PRO-2 score and bowel urgency in the last 3 days before the visit.
* A sigmoidoscopy with 2 biopsies (taken in the most inflamed area) as well as a fecal calprotectin measurement will be performed during the inclusion visit. The sigmoidoscopy procedure will be scored locally by the gastroenterologist with the endoscopic Mayo score and the UCEIS score. The Geboes score will be calculated centrally.
* The patient will complete the Short Health Scale and the Medication Adherence Report Scale.
* Biochemistry (including hematocrit, hemoglobin, platelets count, leucocytes, CRP, urea and serum creatinine) is not obligatory, but if it is planned in the routine management of the patient, these data will be recorded for study purposes.
* In patients not achieving complete endoscopic remission (Endoscopic Mayo subscore \>0), an exploratory questionnaire will be answered by the physician about "physician perspective" regarding the treatment strategy to explore the supposed reasons of the absence of UC remission. Depending on the answer, an exploratory questionnaire can be directed towards the patient exploring the reason for possible low adherence or deliberately refusing other medications.

Eligibility criteria: Inclusion Criteria:

1. Male or female ≥ 18 years
2. Confirmed diagnosis of UC
3. Patients with PRO-2 ≤ 1, with ≤ 1 for stool frequency and 0 for rectal bleeding in the last 3 days before the visit.
4. Recruitment during a routine follow-up visit.
5. Subjects to whom 5-ASA treatment has been prescribed for at least 6 months (any type of oral and/or rectal 5 ASA, any dosage) and with the dose of 5-ASA stable for at least 2 weeks (including suppositories) prior to inclusion.
6. Prescription of 5-ASA is within the locally approved Summary of Product Characteristics (SmPCs)
7. Subjects free of concomitant UC medication (corticosteroids, immunomodulators, biologics, JAK inhibitors, S1PR modulator or investigational drugs) for at least 3 months
8. Subject or the subject's legally acceptable representative have the capacity to understand and (voluntary) sign an informed consent form
9. Be able to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria:

Any subject who meets one of the following criteria will not qualify for entry in the study:

1. Subjects currently treated by immunomodulators, biologics, JAK inhibitors, S1PR modulator and investigational drugs and within the last three months. A history of immunomodulator or biologic or JAK inhibitor or S1PR modulator and investigational drugs use in the past is not an exclusion criteria.
2. Subjects recruited during hospitalization, or via the urgency department for active UC, or during an unscheduled visit for emergency reasons.
3. UC patients with a total colectomy, with or without IPAA
4. Patients with indetermined colitis (IBDU)
5. Women that are pregnant

Primary outcomes:
measure: Complete clinical remission
timeFrame: week 0
measure: Endoscopic remission
timeFrame: week 0
measure: Histological remission
timeFrame: week 0
measure: Deep remission
timeFrame: week 0
Secondary outcomes:
measure: Demographic factors associated to the absence of deep remission
timeFrame: week 0
measure: Disease characteristics associated to the absence of deep remission
timeFrame: week 0
measure: Medical history associated to the absence of deep remission
timeFrame: week 0
measure: Medication history associated to the absence of deep remission
timeFrame: week 0
measure: Disease activity based on PRO-2 score associated to the absence of deep remission
timeFrame: week 0
measure: Disease activity based on bowel urgency associated to the absence of deep remission
timeFrame: week 0
measure: Disease activity based on endoscopic score associated to the absence of deep remission
timeFrame: week 0
measure: Disease activity based on histological Geboes score associated to the absence of deep remission
timeFrame: week 0
measure: Disease activity based on objective markers associated to the absence of deep remission
timeFrame: week 0
measure: Adherence associated to the absence of deep remission
timeFrame: week 0
measure: The percentage of adherent patients on 5-ASA medications
timeFrame: week 0
measure: The impact of adherence on the remission status
timeFrame: week 0
measure: The percentage of prescription of the different 5-ASA regimens
timeFrame: week 0
measure: The impact of the prescription rate of the different 5-ASA regimens on the remission status
timeFrame: week 0
measure: Quantification of the quality of life of the patients with UC on 5-ASA
timeFrame: week 0
measure: Correlation of the quality of life scores with the level of remission
timeFrame: week 0
measure: The factors associated with non-deep remission coming from either physician management or patient perception
timeFrame: week 0
Other outcomes:
Locations:
city: Bonheiden
country: Belgium
facility: Imelda Ziekenhuis
city: Bruxelles
country: Belgium
facility: Hôpital Erasme
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg
city: Gent
country: Belgium
facility: AZ Sint-Lucas Gent
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Liège
country: Belgium
facility: CHU de Liège - Site Sart Tilman
city: Liège
country: Belgium
facility: Groupe santé CHC Clinique du MontLégia
city: Malle
country: Belgium
facility: AZ Voorkempen Malle
city: Oostende
country: Belgium
facility: AZ Damiaan
city: Roeselare
country: Belgium
facility: AZ Delta
city: Tielt
country: Belgium
facility: Sint-Andries ziekenhuis Tielt
city: Tongeren
country: Belgium
facility: AZ Vesalius
city: Turnhout
country: Belgium
facility: AZ Turnhout
city: Yvoir
country: Belgium
facility: CHU UCL Namur -Site Mont Godinne
Study officials:
affiliation: Study Principal Investigator
name: Catherine Reenaers, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: