Guselkumab, Ulcerative Colitis (Disorder)
Conditions
Keywords
moderate-to-severe ulcerative colitis, Guselkumab, efficacy and safety, real-world study
Brief summary
In a real-world setting, this study systematically evaluates the clinical efficacy and safety of guselkumab (GUS) in the treatment of ulcerative colitis (UC), encompassing multi-dimensional outcomes including clinical remission, biochemical remission, endoscopic remission, histologic healing, and intestinal ultrasound changes.
Interventions
DRUGGuselkumab
All the patients receive GUS (IV) 200 mg induction therapy at weeks 0, 4, and 8, and who met the criteria for clinical symptom remission, biochemical remission, and improvement in intestinal ultrasound based on the clinical assessment at week 12, proceeded to receive GUS (SC) 100 mg every 8 weeks as maintenance therapy. Patients who did not meet the above criteria received GUS (SC) 200 mg every 4 weeks as maintenance therapy. At week 24, based on clinical and endoscopic evaluations, patients who achieved endoscopic remission were switched to GUS (SC) 100 mg every 8 weeks for maintenance, while those who did not achieve endoscopic remission continued to receive GUS (SC) 200 mg every 4 weeks for maintenance treatment.
Sponsors
Second Affiliated Hospital of Wenzhou Medical University
Xian-Janssen Pharmaceutical Ltd.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years. 2. Diagnosis of ulcerative colitis is established based on clinical manifestations, laboratory findings, colonoscopy, radiological imaging (CT or ultrasound), and histopathological examination. 3. Presence of moderate-to-severe disease activity, defined as a modified Mayo score (MMS) ≥ 5 points, accompanied by a rectal bleeding subscore (RBS) ≥ 1 and a Mayo endoscopic subscore (MES) ≥ 2. 4. Inadequate response or intolerance to at least one conventional therapy (5-aminosalicylates, corticosteroids, or immunosuppressants), as assessed by the investigator according to clinical practice. 5. Based on the research cohort requirements, the GUS real-world cohort may include patients who are biologic-naive, have failed first-line therapy, or have failed multiple lines of therapy. 6. Availability of baseline data for disease activity assessment, including symptom scores (partial Mayo score or PRO2), endoscopic evaluation (MES), biochemical markers (C-reactive protein or fecal calprotectin), or imaging parameters (CT or intestinal ultrasonography). 7. Patients enrolled in the prospective GUS cohort are required to provide written informed consent voluntarily.
Exclusion criteria
1. Diagnosed with other intestinal diseases, such as Crohn's disease, intestinal tuberculosis, infectious colitis, ischemic colitis or other chronic intestinal inflammatory diseases; 2. If there is an active intestinal infection, and the fecal culture or pathogen test shows positive within 8 weeks before the study (including Clostridium difficile, cytomegalovirus, etc.), and the re-examination turns negative without any signs of persistent infection, a re-evaluation can be conducted. 3. Combined with severe infections, malignant tumors, severe liver and kidney dysfunction, or accompanied by active autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis, and Graves' disease that may interfere with disease assessment 4. Those who have undergone total colorectal resection or stoma surgery in the past and whose disease activity cannot be evaluated, or are expected to undergo major intestinal surgery during the study period; 5. Has had a severe allergic reaction to monoclonal antibodies; 6. During pregnancy or lactation (can be recorded as an independent cohort but not included in the primary analysis); 7. Severe absence of baseline and follow-up data makes it impossible to determine efficacy or safety. 8. Currently participating in other interventional clinical trials that may interfere with the results of this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 48-week endoscopic remission | 48 weeks | Assessment was performed using the Mayo endoscopic subscore: endoscopic response was defined as a decrease in the Mayo endoscopic subscore by at least 1 point from baseline or a score of ≤1; endoscopic remission was defined as a Mayo endoscopic subscore of 0. For patients who completed the 48-week treatment, endoscopic scores were evaluated, and the number/proportion of patients achieving endoscopic remission was calculated. |
| 48-week histological remission | 48 weeks | Investigators apply the Geboes score, and histological remission is defined as a Geboes score ≤ 2B.0. The Nancy Histological Index (NHI) is assessed concurrently, with histological remission defined as an NHI = 0 (indicating no active inflammation). Investigators performed histological scoring for patients who completed the 48-week treatment course and evaluated the number/proportion of patients achieving histological remission. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 12-week clinical remission | 12 weeks | Clinical remission in UC is assessed using the partial Mayo score (pMayo) or PRO2. It's defined as either a pMayo score ≤ 2 with no individual subscore \> 1, or meeting the symptomatic remission criteria of PRO2 (indicating improvement in both stool frequency and rectal bleeding scores to the mild or normal range). |
| 12-week biochemical remission | 12 weeks | 1. CRP normalization (≤5 mg/L) or reduction by ≥50% from baseline. 2. Fecal calprotectin (FC) reduction to \<250 μg/g or reduction by ≥50% from baseline. |
| 12-week intestinal ultrasound response | 12 weeks | Response to intestinal ultrasound (IUS) was defined as meeting both of the following criteria: 1) a decrease in bowel wall thickness (BWT) by ≥25% or a reduction of ≥1 mm from baseline; and 2) a reduction in blood flow signal (Limberg score) by ≥1 grade. |
| 24-week and 48-week intestinal ultrasound response | 24 weeks; 48 weeks | Intestinal ultrasound (IUS) remission was defined as meeting both of the following criteria: 1) bowel wall thickness (BWT) ≤ 3 mm; and 2) no detectable blood flow signal (Limberg grade 0). |
| 24-week endoscopic response and remission | 24 weeks | Endoscopic response in UC was defined as a Mayo Endoscopic Score (MES) reduction of ≥1 point from baseline or a score of ≤1. Endoscopic remission was defined as an MES of 0. |
| 24-week and 48-week Corticosteroid-free remission rate | 24 weeks; 48 weeks | Corticosteroid-free remission, a core treatment target recommended by the STRIDE-II guidelines, reflects a patient's ability to maintain clinical remission without the aid of systemic glucocorticoids. It is defined as achieving clinical remission at the assessment timepoint without the use of oral or intravenous glucocorticoids for at least 12 weeks prior to assessment. The proportion of UC patients achieving corticosteroid-free remission was documented for evaluation of the sustainability and steroid-sparing capacity of the treatment. |
| 48-week drug persistence rate | 48 weeks | Drug persistence rate is defined as the proportion of patients who continue to receive a given drug after initiation of treatment. It reflects the tolerability, adherence, and long-term benefit of the therapy, and serves as a core indicator in real-world evidence (RWE) studies. Patients who discontinue treatment due to objective non-medical reasons (e.g., relocation, change of healthcare system) may be excluded in sensitivity analyses. |
| Hospitalization and surgery rates at week 48 | 48 weeks | 1. Incidence of hospitalizations due to inadequate disease control and cumulative length of hospital stay. 2. Incidence and timing of intestinal resection or related surgeries performed due to disease activity or complications. |
| Impact of Prior Biologic Exposure on Efficacy | Efficacy comparisons were compared at all key study visits: baseline, week 12, week 24, and week 48. | The clinical, endoscopic, intestinal ultrasound (IUS), and biochemical improvements were compared between biologic-naïve patients and patients with prior biologic therapy failure or intolerance. This analysis was performed to determine whether previous biologic exposure influences treatment outcomes. |
| Inflammatory Bowel Disease Questionnaire (IBD-Q) scores at week 48 | 48 weeks | 1. A total score increase of ≥16 points from baseline is considered a clinically significant improvement. 2. Restoration to a normal or near-normal level (score ≥ 170) from an active disease state is considered achievement of quality of life remission. |
| Exploratory Study (Comparing the Efficacy of GUS and VDZ) | Efficacy comparisons were compared at all key study visits: baseline, week 12, week 24, and week 48 | Patients with ulcerative colitis (UC) who had previously received vedolizumab (VDZ) treatment and had complete baseline and follow-up data were retrospectively enrolled from the study center. Propensity score matching analysis was performed to compare the effects of GUS and VDZ on multidimensional outcomes in moderate-to-severe UC in a real-world setting, including clinical response and remission, endoscopic remission, histological remission, and treatment persistence. |
Countries
China
Contacts
CONTACTYi Jiang, Doctor of Medicine
CONTACTguolong Ma, Master of Medicine
PRINCIPAL_INVESTIGATORYi Jiang
Second Affiliated Hospital of Wenzhou Medical University
Outcome results
None listed