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.
