Guselkumab Vs Ustekinumab in Stricturing Crohn's Disease
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18-80
SponsorSecond Affiliated Hospital, School of Medicine, Zhejiang University
About this trial
This study intends to select patients with confirmed moderate-to-severe Crohn's disease (CD) and obstructive symptoms of intestinal stenosis, who have clear evidence of lumen stenosis caused by the disease itself through radiography or endoscopy. After the informed consent of the patients, comprehensive drug therapy with Guselkumab or Ustekinumab as the mainstay was performed. The basic information and medical history of the patients were collected, and the treatment process of the patients was followed up and recorded, and the drug regimen was adjusted according to the physician's experience and judgment. At different follow-up time points, blood, feces, tissue and other specimens of patients were collected according to the situation, and gastrointestinal endoscopy, imaging examination, laboratory index examination, self-assessment of subjects' symptoms, and nutritional risk screening were performed on the patients. This study evaluated the CD disease activity, obstructive symptoms, and radiographic or endoscopic remission in patients at different follow-up time points, and comprehensively evaluated the efficacy of ustekinumab in relieving stenotic CD and its related factors.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Confirmed patients with moderate-to-severe Crohn's disease (CD), aged 18 to 80 years, receiving treatment with Guselkumab or Ustekinumab.
Presence of obstructive symptoms consistent with chronic or subacute intestinal obstruction within the past 8 weeks, with confirmed postprandial abdominal pain attributable to strictures, with the exclusion of: ① mild to moderate pain (postprandial abdominal pain or abdominal pain exacerbated by diet, ameliorated with abdominal bowel sounds) without nausea, vomiting or abdominal colic; ② dietary restrictions unrelated to abdominal pain.
Enteric computed tomography (CT): Presence of intestinal strictures on enteric CT, with two of the three following findings at the stricture site compared with the adjacent proximal bowel: ① a >50% reduction in luminal diameter; ② a >25% increase in bowel wall thickness; ③ pre-stenotic dilation >2.5 cm.
Endoscopic examination: Intestinal strictures that are impassable to the endoscope.
Disqualifiers
Patients with severe disease requiring emergency surgery or endoscopic therapeutic intervention, or those judged by the attending clinician to need a switch of medication or elective surgery within 2 months, such as those with acute severe intestinal obstruction, perforation, intra-abdominal abscess, intra-abdominal adhesion, and other conditions leading to obstruction, hemorrhage, infection, etc.
Intestinal obstruction, intra-abdominal abscess, isolated intestinal stricture and other lesions secondary to surgery.
Patients who have received definitive therapeutic interventions for strictures within the past 6 months, such as endoscopic balloon dilation, stricture incision, intestinal stricture plasty, surgical/manual anal dilatation, etc.
Severe patients who remain unable to take oral intake despite enteral nutrition (EN) administration for more than 2 months.
Trial population
Patients who will initially receive Guselkumab or Ustekinumab for the treatment of stricturing Crohn's disease
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Guselkumab (GUS)
Drug① Induction phase (Weeks 1-12): GUS 200 mg intravenously (IV) every 4 weeks for 3 doses, followed by a maintenance phase with GUS 100 mg subcutaneously (SC) every 8 weeks (for patients with all indicators within the normal range). ② Maintenance phase: Dosing adjustments shall be optimized based on the clinician's experience: If any disease activity occurs during the maintenance phase (e.g., suboptimal levels of CRP or FCP), administer GUS 200 mg SC every 4 weeks, or GUS 100 mg SC every 8 weeks plus enteral nutrition accounting for no more than 50% of the total daily energy intake. In case of persistent disease activity, administer intensive intravenous infusion of GUS 200 mg for 3 doses based on patient needs and shared decision-making.
Ustekinumab (UST)
Drug① Induction phase (Weeks 1-8): UST 6 mg/kg intravenously (IV) for 1 dose, followed by UST 90 mg subcutaneously (SC) every 8 weeks. A maintenance dose of 90 mg SC shall be administered every 8 or 12 weeks thereafter on a case-by-case basis. ② Experience-based dosing optimization and adjustment: If C-reactive protein (CRP) or fecal calprotectin (FCP) levels are suboptimal, two treatment approaches shall be adopted based on patient needs and shared decision-making: intravenous intensification therapy (predominantly 2 to 3 IV doses, i.e., 260 mg or 390 mg, with a follow-up visit at 8 weeks); or 90 mg SC with a shortened administration interval (with a follow-up visit at 4 to 6 weeks). ③ The duration of Exclusive Enteral Nutrition (EEN) use shall not exceed 2 weeks. If enteral nutrition support is required beyond 2 weeks, switch to Partial Enteral Nutrition (PEN), which shall account for less than 50% of the patient's total energy requirement.
Treatment groups
100 Participants
are divided into 2 treatment groupsGroup A: GUS1 intervention
Group B: UST1 intervention
Trial outcomes
Primary outcomes
1
Continuation of ustekinumab
The primary endpoint was the success at week 52, defined as ustekinumab continuation with all the following criteria: (1) no use of a prohibited treatment (corticosteroids after the eight week following inclusion, parenteral nutrition, other anti-TNFs); (2) no endoscopic dilation; (3) no bowel surgery for resection of small bowel stricture; (4) no severe adverse events leading to ustekinumab withdrawal and (5) no study withdrawal whatever the reason.
Time frame
up to 52 weeksSecondary outcomes
1
CT stricture improvement
CT stricture improvement was defined as resolution of prestenotic dilatation (small bowel diameter \<3.0 cm); stricture resolution (normal bowel wall thickness and luminal diameter with absence of prestenotic dilation; and reduced stricture length by ≥1 mm). Intestinal ultrasound stricture improvement included normalisation of prestenotic dilation (\<3.0 cm) or reduction in prestenotic dilation (≥50%).
Time frame
at Week 0 and 522
General health improvement
General health improvement was measured by patient reported outcomes through health-related quality of life (Inflammatory Bowel Disease (IBD) Quality of Life Questionnaire).
Time frame
at Week 0, 8, 24 and 523
Number of Participants with surgery
Surgical rates during follow-up included the proportion of patients undergoing any surgery for endoscopic dilatation and stricture resection.
Time frame
up to 52 weeksSponsors and contacts
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Second Affiliated Hospital, School of Medicine, Zhejiang University
Lead sponsor
People's Hospital of Chongqing
Collaborator
Source ClinicalTrials.gov