Crohn's Disease
Conditions
Keywords
Crohn's disease, IL-23 inhibitor, TNF inhibitor, Bio-naive, Real-world study, Observational cohort, Clinical remission, Endoscopic remission
Brief summary
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
Detailed 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.
Interventions
DRUGIL-23 inhibitor
Participants 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.
DRUGTNF inhibitors
Participants 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.
Sponsors
Sixth Affiliated Hospital, Sun Yat-sen University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18 to 75 years 2. Diagnosis of Crohn's disease based on clinical presentation, endoscopy, imaging, and/or histopathology, consistent with ECCO criteria or Chinese IBD consensus criteria 3. 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 4. Planned initiation of IL-23 inhibitor therapy in routine clinical practice, including guselkumab or risankizumab, with no prior exposure to IL-23 inhibitors 5. 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 6. 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 7. Able to understand the study procedures, provide written informed consent, and comply with follow-up and biospecimen collection requirements 8. 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
1. Prior exposure to any IL-23 inhibitor, including guselkumab, risankizumab, mirikizumab, or other IL-23-targeted agents 2. 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 3. Crohn's disease requiring urgent surgery or associated with severe complications, including active bowel perforation, uncontrolled fistula with severe infection, or complete bowel obstruction 4. 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 5. Current or prior malignancy, except adequately treated non-melanoma skin cancer or cervical carcinoma in situ with no evidence of recurrence 6. Pregnancy, breastfeeding, or planned pregnancy during the study period 7. 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 8. Inability to complete follow-up, poor compliance, or recent participation in another interventional clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Remission Rate | Week 12 | Proportion of participants achieving clinical remission at Week 12, defined as a Crohn's Disease Activity Index (CDAI) score \<150. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response Rate | Weeks 12 and 52 | 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. |
| Endoscopic Remission Rate | Weeks 12 and 48 | Proportion of participants achieving endoscopic remission, defined as a Simple Endoscopic Score for Crohn's Disease (SES-CD) score ≤3. |
| Endoscopic Response Rate | Weeks 12 and 52 | Proportion of participants achieving endoscopic response, defined as a decrease of more than 50% in SES-CD from baseline or SES-CD ≤3. |
| Corticosteroid-Free Clinical Remission Rate | Weeks 12 and 52 | Proportion of participants achieving clinical remission without corticosteroid therapy, defined as CDAI \<150 in the absence of systemic corticosteroid use. |
| Corticosteroid-Free Endoscopic Remission Rate | Weeks 12 and 52 | Proportion of participants achieving endoscopic remission without corticosteroid therapy, defined as Simple Endoscopic Score for Crohn's Disease (SES-CD) score ≤3 in the absence of systemic corticosteroid use. |
| Deep Remission Rate | Weeks 12 and 52 | Proportion of participants achieving both clinical remission and endoscopic remission. |
| Mucosal Healing Rate | Weeks 12 and 52 | Proportion of participants achieving mucosal healing, defined as Simple Endoscopic Score for Crohn's Disease (SES-CD) score \<3 with an ulcer subscore of 0, excluding the effect of stricture scoring. |
| Bowel Ultrasound Inflammatory Improvement Rate | Weeks 12 and 52 | Proportion of participants achieving bowel ultrasound inflammatory improvement, defined as bowel wall thickness ≤3 mm and/or a decrease of at least 1 grade in bowel wall vascularity assessed by Limberg score, compared with baseline. |
| C-Reactive Protein Normalization Rate | Weeks 12 and 52 | Proportion of participants achieving normalization of C-reactive protein (CRP) at each assessment time point, defined as CRP within the normal range according to the local laboratory standard. |
| Fecal Calprotectin Normalization Rate | Weeks 12 and 52 | Proportion of participants achieving normalization of fecal calprotectin (FC) at each assessment time point, defined as FC \<250 μg/g. |
| Trough Concentration of IL-23 Inhibitor | Weeks 12 and 52 | Measured trough concentration of IL-23 inhibitor therapy at each assessment time point, if available. Exploratory analyses will assess its association with clinical and endoscopic outcomes. |
| Adverse Events | Weeks 12 and 52 | Incidence of adverse events from treatment initiation through Week 12 and through Week 52, graded according to CTCAE version 5.0. |
| Serious Adverse Events | Weeks 12 and 52 | Incidence of serious adverse events from treatment initiation through Week 12 and through Week 52, defined as events resulting in death, are life-threatening, require unplanned hospitalization or prolongation of hospitalization, result in persistent or significant disability, or are considered medically important by the investigator. |
| Special Safety Events | Weeks 12 and 52 | Incidence of prespecified safety events of special interest from treatment initiation through Week 12 and through Week 52, including serious infection, opportunistic infection, tuberculosis, herpes zoster, thrombotic events, and liver function abnormalities. |
Countries
China
Contacts
CONTACTWei Wang, MD & PhD
PRINCIPAL_INVESTIGATORWei Wang, MD
The Sixth Affiliated Hospital, Sun Yat-sen University
Outcome results
None listed