Overview
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
Description
This is a prospective, multicenter, real-world observational cohort study designed to evaluate the effectiveness and safety of IL-23 inhibitors in adults with active Crohn's disease in routine clinical practice. The primary study population consists of patients who initiate treatment with an IL-23 inhibitor, including guselkumab or risankizumab, as part of physician-directed standard care. Participants will be consecutively enrolled and followed according to the study protocol.
This is not a head-to-head randomized controlled trial. Treatment is not assigned by the study protocol; instead, therapy is selected by treating physicians in routine clinical practice. In addition to the primary IL-23 inhibitor cohort, a concurrent prospective cohort of bio-naive patients initiating TNF inhibitor therapy will be enrolled during the same study period for a nested comparative analysis. This comparative cohort is intended to support evaluation of comparative effectiveness and safety between bio-naive IL-23 inhibitor-treated participants and bio-naive TNF inhibitor-treated participants.
Eligible participants must have active Crohn's disease with objective evidence of intestinal inflammation, as defined by protocol-specified clinical, endoscopic, imaging, and/or biomarker criteria. For the IL-23 inhibitor cohort, both biologic-naive and biologic-experienced patients may be included, provided they have not previously received IL-23 inhibitor therapy. For the concurrent TNF inhibitor comparative cohort, participants must be bio-naive and must otherwise meet the relevant protocol-defined eligibility criteria.
The primary outcome is the clinical remission rate at Week 12, defined as a Crohn's Disease Activity Index (CDAI) score of less than 150. Secondary outcomes include clinical response, endoscopic remission, endoscopic response, PRO-2 remission, corticosteroid-free clinical remission, corticosteroid-free endoscopic remission, deep remission, mucosal healing, bowel ultrasound inflammatory improvement, C-reactive protein normalization, fecal calprotectin normalization, and safety outcomes assessed during induction and maintenance follow-up. Safety assessments include adverse events, serious adverse events, special safety events, and treatment discontinuation or switching.
Participants will undergo protocol-defined follow-up assessments during induction and maintenance, including evaluations at baseline, Week 12 and Week 52, as available in routine clinical practice. Assessments may include symptom evaluation, laboratory testing, endoscopy, bowel ultrasound, and other clinically indicated imaging studies. Optional biospecimen collection may include blood, stool, and clinically available intestinal tissue samples.
Exploratory analyses will examine integrated multi-omics features associated with treatment response, including fecal microbiome, blood and fecal metabolomic, and intestinal tissue transcriptomic data in participants with available samples. These analyses are intended to identify candidate biologic features associated with clinical remission, endoscopic outcomes, biomarker improvement, and safety outcomes over time.
This study is intended to generate prospective real-world evidence regarding the effectiveness and safety of IL-23 inhibitors in active Crohn's disease and to provide additional comparative evidence from a concurrent prospective bio-naive TNF inhibitor cohort in nested analyses.
Eligibility
Inclusion Criteria:
- 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
- Prior treatment history for the IL-23 inhibitor cohort may include biologic-naive or biologic-experienced patients; prior exposure to TNF inhibitors, vedolizumab, or ustekinumab is permitted
- If receiving concomitant medications, doses should be stable for at least 2 to 4 weeks before enrollment, including oral corticosteroids, azathioprine, 6-mercaptopurine, methotrexate, or 5-aminosalicylic acid
- Able to understand the study procedures, provide written informed consent, and comply with follow-up and biospecimen collection requirements
- Additional criteria for the concurrent prospective TNF inhibitor cohort used in the nested comparative analysis: (1) Participants must be bio-naive, defined as no prior exposure to any biologic agent (including TNF inhibitors, vedolizumab, ustekinumab, etc.) or targeted small-molecule therapy (such as JAK inhibitors), (2) Participants must also meet Inclusion Criteria 1, 2, 3, 6, and 7 above, (3) Participants must be planned to initiate TNF inhibitor therapy in routine clinical practice
Exclusion Criteria:
- 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
- Current or prior malignancy, except adequately treated non-melanoma skin cancer or cervical carcinoma in situ with no evidence of recurrence
- Pregnancy, breastfeeding, or planned pregnancy during the study period
- Severe systemic disease or other condition that, in the investigator's judgment, makes participation unsuitable, including severe cardiac, hepatic, or renal dysfunction, uncontrolled autoimmune disease, or psychiatric disease affecting adherence
- Inability to complete follow-up, poor compliance, or recent participation in another interventional clinical trial
