The Application of Transcriptomics in the Treatment of Ulcerative Colitis With Ustekinumab

The Application of Transcriptomics for Establishing Potential Prognostic Markers of Response to Treatment of Ulcerative Colitis With Ustekinumab

The investigators hope that the present study will highlight new transcriptomic prognostic markers of response to Ustekinumab with the ultimate goal of individualizing treatment and making a more targeted selection of UC patients who will benefit from this biological agent.

Study Overview

• Status: Active, not recruiting
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Ustekinumab

Detailed Description

Introduction: Optimizing treatment with biological agents is an ideal goal for patients with ulcerative colitis (UC). At present, there are insufficient prognostic markers of response to each biological agent, which makes it difficult to individualize treatment. Recent data suggest that mucosal inflammation patterns and serum cytokine profiles differ between patients who respond and those who do not. These studies mainly focused on anti-TNFα agents and Vedolizumab, while there are no corresponding data for Ustekinumab, which is a monoclonal antibody to interleukins 12 and 23 and has recently been approved for the treatment of patients with UC.

Aim of the study: To highlight prognostic markers of response (clinical and endoscopic) to Ustekinumab, in patients with UC, utilizing information from their transcriptome before starting treatment.

Methods: This is a prospective, single-center cohort study that will evaluate transcriptomic markers of response to Ustekinumab in patients with active UC. The diagnosis of the disease will be based on the established clinical, endoscopic and histological criteria. The patients' recruitment will begin in April 2022, while their consent will be required. The duration of follow-up of patients will be at least 6 months from the start of biological treatment. Patients will undergo endoscopy (sigmoidoscopy or total colonoscopy) with a biopsy of the orthosigmoid before the start of biological treatment and a repeat endoscopy 6 months later. The RNA profile of the patients will be recorded after isolation of the total RNA from colon biopsies. Then, using biostatistics, the transcriptomic profiles of patients who responded to Ustekinumab and those who did not respond to 6 months of treatment, will be compared.

• Study Type: Observational
• Enrollment (Actual): 38

Contacts and Locations

Study Locations

• Greece
  • Attiki
    • Athens, Attiki, Greece, 10676
      • Evangelismos Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients with Ulcerative Colitis treated with Ustekinumab

Description

Inclusion Criteria:

• Active UC in accordance with applicable diagnostic criteria [25] •
• Aged 18 or above

Exclusion Criteria:

• Prior surgical history for UC
• Toxic megacolon
• Infectious complications (Cl. Difficile, CMV infection)
• Patients who received any approved biologic agent (e.g. Infliximab, adalimumab, vedolizumab, golimumab) within the previous 8 weeks or any investigational biologic or other agent in the last 35 days

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ulcerative colitis patients treated with ustekinumab; Patients with Ulcerative Colitis treated with ustekinumab	Drug: Ustekinumab; Patients with ulcerative colitis treated with ustekinumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the rate of clinical remission	Total Mayo score of 2 or lower and no subscore higher than 1	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endoscopic response rate	Reduction of the endoscopic Mayo subscore ≥1	6 months
Clinical response rate	Reduction in the Mayo score of at least 3 points and a decrease of at least 30% from the baseline score, with a decrease of at least 1 point on the rectal bleeding subscale or an Absolute rectal bleeding score of 0 or 1	6 months
Endoscopic remission rate	Endoscopic Mayo subscore 0	6 months

Collaborators and Investigators

• Sponsor: Evangelismos Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2022
• Primary Completion (Actual): October 31, 2023
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: May 8, 2023
• First Submitted That Met QC Criteria: June 8, 2023
• First Posted (Actual): June 9, 2023

Study Record Updates

• Last Update Posted (Estimated): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Dermatologic Agents; Ustekinumab
• Other Study ID Numbers: 479/15-12-2022

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No