Real-World Study of IL-23 Inhibitors in Active Crohn's Disease
ConditionCrohn's Disease
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18-75
SponsorSixth Affiliated Hospital, Sun Yat-sen University
About this trial
The goal of this observational study is to learn about the effectiveness and safety of IL-23 inhibitors in adults with active Crohn's disease in real-world clinical practice. The main questions it aims to answer are:
* What proportion of participants achieve clinical remission at Week 12 after starting treatment with an IL-23 inhibitor? * What are the clinical, endoscopic, biomarker, imaging, and safety outcomes during induction and maintenance treatment?
This is not a head-to-head randomized study. Treatments are selected by treating physicians as part of routine clinical care. For a nested comparative analysis, bio-naive participants treated with IL-23 inhibitors will be compared with a concurrent prospective cohort of bio-naive participants treated with TNF inhibitors to evaluate comparative effectiveness and safety.
Participants will:
* Receive treatment chosen by their treating physicians as part of routine clinical care, including IL-23 inhibitors or TNF inhibitors * Attend study follow-up visits during induction and maintenance, including assessments at baseline, Week 12 and Week 52 * Undergo routine clinical evaluations, which may include symptom assessment, laboratory tests, endoscopy, and imaging, as available * Be monitored for adverse events and treatment changes during the study * Optionally provide blood, stool, and other available samples for exploratory biomarker, microbiome, metabolomic, and other multi-omics analyses related to treatment response
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age 18 to 75 years
Diagnosis of Crohn's disease based on clinical presentation, endoscopy, imaging, and/or histopathology, consistent with ECCO criteria or Chinese IBD consensus criteria
Active Crohn's disease with a baseline Crohn's Disease Activity Index (CDAI) score of 150 to 450, and at least one of the following objective inflammatory findings: (1) Endoscopic activity within 1 month before enrollment, defined as Simple Endoscopic Score for Crohn's Disease (SES-CD) >=6 for ileocolonic or colonic disease, or SES-CD >=4 for isolated ileal disease, (2) Active intestinal inflammation on bowel ultrasound, computed tomography enterography (CTE), or magnetic resonance enterography (MRE), (3) Serum C-reactive protein (CRP) above the upper limit of normal, (4) Fecal calprotectin (FC) >=250 ug/g
Planned initiation of IL-23 inhibitor therapy in routine clinical practice, including guselkumab or risankizumab, with no prior exposure to IL-23 inhibitors
Disqualifiers
Prior exposure to any IL-23 inhibitor, including guselkumab, risankizumab, mirikizumab, or other IL-23-targeted agents
Diagnosis of inflammatory bowel disease other than Crohn's disease, or other intestinal disorders that may confound diagnosis, including ulcerative colitis, IBD-unclassified, intestinal tuberculosis, ischemic colitis, or radiation enteritis
Crohn's disease requiring urgent surgery or associated with severe complications, including active bowel perforation, uncontrolled fistula with severe infection, or complete bowel obstruction
Active infection or high-risk infectious condition, including active tuberculosis, latent tuberculosis without appropriate prophylaxis, active hepatitis B or C, HIV infection, or severe/recurrent infection history
Trial population
Adults with active Crohn's disease consecutively enrolled from participating centers in routine clinical practice. The main study population is a prospective multicenter cohort of patients initiating IL-23 inhibitor therapy, including guselkumab or risankizumab. A concurrent prospective cohort of bio-naive patients initiating TNF inhibitor therapy will also be enrolled for a nested comparative analysis. Participants must have objective evidence of active disease and satisfy protocol-defined eligibility criteria.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
IL-23 inhibitor
DrugParticipants in this observational study receive IL-23 inhibitor therapy as part of routine clinical care, including guselkumab or risankizumab according to local practice and physician judgment. Treatment is not assigned by the study protocol. This drug exposure is the primary focus of the study for evaluation of effectiveness and safety in active Crohn's disease.
TNF inhibitors
DrugParticipants in the comparative cohort receive TNF inhibitor therapy as part of routine clinical care, including infliximab or adalimumab according to local practice and physician judgment. Treatment is not assigned by the study protocol. This drug exposure is included for the concurrent prospective comparative cohort used in the nested comparative analysis.
Treatment groups
665 Participants
are divided into 2 treatment groupsGroup A: IL-23 Inhibitor Cohort1 intervention
Group B: TNF Inhibitor Comparative Cohort1 intervention
Trial outcomes
Primary outcomes
1
Clinical Remission Rate
Proportion of participants achieving clinical remission at Week 12, defined as a Crohn's Disease Activity Index (CDAI) score \<150.
Time frame
Week 12Secondary outcomes
1
Clinical Response Rate
Proportion of participants achieving clinical response, defined as a decrease of at least 100 points in Crohn's Disease Activity Index (CDAI) from baseline or CDAI \<150.
Time frame
Weeks 12 and 522
Endoscopic Remission Rate
Proportion of participants achieving endoscopic remission, defined as a Simple Endoscopic Score for Crohn's Disease (SES-CD) score ≤3.
Time frame
Weeks 12 and 483
Endoscopic Response Rate
Proportion of participants achieving endoscopic response, defined as a decrease of more than 50% in SES-CD from baseline or SES-CD ≤3.
Time frame
Weeks 12 and 524
Corticosteroid-Free Clinical Remission Rate
Proportion of participants achieving clinical remission without corticosteroid therapy, defined as CDAI \<150 in the absence of systemic corticosteroid use.
Time frame
Weeks 12 and 52Other outcomes
1
Integrated Multi-Omics Features Associated With Treatment Response
Exploratory evaluation of integrated multi-omics features, including fecal microbiome, blood and fecal metabolomic, and intestinal tissue transcriptomic data, and their associations with treatment response. Analyses will assess changes from baseline to Weeks 12 and 52 and identify candidate biologic features associated with clinical remission, endoscopic outcomes, biomarker improvement, and safety outcomes in participants with available samples.
Time frame
Baseline, Week 12, and Week 52Sponsors and contacts
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Source ClinicalTrials.gov