Biomarker, Fecal Calprotetin, FIT, Ulcerative Colitis (UC)
Conditions
Keywords
ulcerative colitis, fecal calprotectin, FIT, biologic-naive
Brief summary
This multicenter prospective cohort study aims to evaluate whether a \>50% decrease or normalization of both quantitative fecal immunochemical test (qFIT) and fecal calprotectin (FC) levels at 2 weeks after starting conventional therapy (mesalazine or corticosteroids) can predict clinical relapse or need for biologic/JAK inhibitor therapy escalation by 52 weeks in biologic-naive patients with active ulcerative colitis (UC). Secondary objectives include assessing predictive value at 4 weeks, building dynamic prediction models, conducting health economic evaluation (Number Needed to Test, NNT), and exploring baseline predictors of early biomarker response. Patients will be observed during standard care with stool samples collected at Weeks 0, 2, and 4. Biomarker results will be blinded to clinicians/patients until study completion.
Detailed description
This is a prospective, observational cohort study conducted across multiple centers in China. Biologic-naive UC patients (Mayo Endoscopic Subscore ≥2) initiating conventional therapy (mesalazine or corticosteroids) will be enrolled. Stool samples for quantitative FIT (qFIT) and fecal calprotectin (FC) will be collected at Baseline (Week 0) , Week 2 (±3 days) , and Week 4 (±3 days) . Patients are classified at Week 2: Group A (Rapid Responders): Both qFIT & FC decrease \>50% from baseline OR normalize. Group B (Slow/Non-Responders): Either qFIT or FC decrease ≤50%. The primary endpoint is the composite event rate (clinical relapse OR treatment escalation to biologics/JAK inhibitors) by Week 52 (±2 weeks) . Clinical relapse is defined as an increase ≥2 points in partial Mayo score (excluding endoscopy) with a rectal bleeding subscore ≥1 requiring therapy adjustment. Treatment escalation occurs per standardized criteria (steroid-refractoriness or dependence). Secondary endpoints include time-to-event, corticosteroid-free remission, mucosal healing at Week 52, predictive model performance (AUC, sensitivity, specificity), NNT calculation, and baseline predictors.
Interventions
DIAGNOSTIC_TESTFC and FIT TEST at WEEK0 2 4
FC and FIT TEST at WEEK0 2 4
Sponsors
Qilu Hospital of Shandong University
Qilu Hospital of Shandong University (Qingdao)
Dezhou Hospital Qilu Hospital of Shandong University
JiNing NO.1 People Hospital
Zaozhuang Municipal Hospital
caoxian chinese medicine hospital
longkou chinsese medicine hospital
Shouguang people's Hospital
Weihai Municipal Hospital
Liaocheng People's Hospital
ZhangQiu Yile Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-75 years. * Established diagnosis of Ulcerative Colitis (UC) confirmed by clinical, endoscopic, and histopathological criteria. * Endoscopic disease activity (Mayo Endoscopic Subscore ≥ 2) confirmed by colonoscopy during screening. * Biologic-naive (no prior exposure to any biologic agent \[e.g., infliximab, adalimumab, vedolizumab, ustekinumab\] or JAK inhibitor). * No use of systemic corticosteroids (oral or intravenous) within 4 weeks prior to Baseline (Week 0) visit. * If using oral or rectal mesalazine/5-ASA preparations, dose must have been stable for ≥2 weeks prior to Baseline (Week 0). Willing and able to provide written informed consent.
Exclusion criteria
* Diagnosis or high suspicion of Crohn's disease, ischemic colitis, infectious colitis, radiation colitis, intestinal tuberculosis, or other types of colitis. Presence of other conditions clearly causing intestinal bleeding (e.g., acute hemorrhoidal bleeding, colorectal cancer, large colorectal polyps \>1cm, intestinal vascular malformations). * Untreated systemic conditions that may cause intestinal bleeding (e.g., thrombocytopenia \[PLT \<50 x 10\^9/L\], severe coagulopathy). * Regular use of antiplatelet agents (e.g., aspirin, clopidogrel) or anticoagulants (e.g., warfarin, rivaroxaban). * Pregnancy or lactation. * Any other condition deemed by the investigator to make the patient unsuitable for study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite Endpoint Rate (Clinical Relapse OR Treatment Escalation) | From enrollment to Week 52 (±2 weeks) | Proportion of patients experiencing either: 1) Clinical Relapse: Increase ≥2 points in partial Mayo Score (stool frequency + rectal bleeding + PGA) with rectal bleeding subscore ≥1 requiring therapy adjustment, OR 2) Treatment Escalation: Initiation of any biologic agent (e.g., infliximab, adalimumab, vedolizumab, ustekinumab) or JAK inhibitor due to steroid-refractoriness (failure to respond by Week 4) or steroid-dependence (relapse during/after steroid taper within 3 months) as per standardized protocol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Composite Endpoint Event | From enrollment to Week 52 (±2 weeks) | — |
| Proportion with Corticosteroid-Free Clinical Remission | Week 52 (±2 weeks) | Partial Mayo Score ≤1 point without corticosteroid use for ≥4 weeks. |
| Diagnostic Performance (AUC) of Week 2 Biomarker Response | Week 2 prediction assessed at Week 52 | Area Under the Receiver Operating Characteristic Curve (AUC) for the Week 2 qFIT+FC combined response (Group A vs B) in predicting the Week 52 composite endpoint. |
| Number Needed to Test (NNT) | Week 52 (±2 weeks) | NNT = 1 / \[Event Rate (Group B) - Event Rate (Group A)\] for the composite endpoint at Week 52. |
| Diagnostic Performance (AUC) of Biomarker Change Slope Models | Weeks 0-2 and Weeks 0-4 slopes assessed at Week 52 | AUC of logistic regression models using the rate of change (Δ/week) of FC and/or qFIT from Week 0 to Week 2 and/or Week 0 to Week 4 for predicting the Week 52 composite endpoint. Sensitivity, specificity, PPV, NPV will also be calculated. |
Countries
China
Contacts
CONTACTYan Zhang, M.D.
Outcome results
None listed