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 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.
Clinical diagnosis of moderate to severe Crohn's disease
Obstructive symptoms within the last eight weeks
A single or several lumen stricture(s) identified by radiological imaging or endoscopy
For strictures identified by CT enterograph defined as a lesion with combination of a reduction of luminal narrowing >50%, an increase in bowel wall thickness >25% relative to non-affected bowel and pre-stricture dilation >3.0 cm
Requirement of urgent surgery or endoscopic intervention within 2 months as judged by the clinician
Symptoms or signs of perforation such as active perianal sepsis, abdominal abscess, intestinal fistula, and abdominal adhesions
Intestinal obstruction caused by surgery, intra-abdominal abscess, isolated intestinal stricture
Effective treatments for stricture in the past half a year, such as endoscopic balloon dilatation, intestinal stricture plasty, surgery/manual anal dilatation, etc.
Participants were adult CD patients treated with their first UST therapy for symptomatic strictures (confirmed on endoscopy or imaging) from centers of IBD at 8 hospitals all over China. This study does not involve the use of vulnerable groups.
Cohort
Prospective
Ustekinumab
DrugThe initial intravenous (IV) infusion with ustekinumab at baseline was weight-adjusted (260 mg ≤55 kg, 390 mg between 55 and 85 kg, 520 mg ≥85 kg). According to the label, the first subcutaneous (SC) 90 mg induction dose was administered at week 8 followed by a maintenance dose of 90 mg SC every 8 or 12 weeks, at the discretion of the physician. 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.
Number of participants with treatment success at week 52
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 biological agents); (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. Clinical improvement was measured by symptoms and clinical remission (Crohn's Disease Activity Index \<150), steroid-free symptom improvement (obstructive symptom score) following initial steroid tapering, Crohn's Disease Obstructive Score (improvement of ≥1 point), treatment failure (defined as bowel obstruction requiring surgery, endoscopic balloon dilation, or persisting symptoms necessitating change in treatment), the need for surgery.
Number of participants with improvement in stricture inflammation and morphology on imaging
CT and MRI 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%). Endoscopic stricture improvement included increased luminal diameter; the ability to pass a standard paediatric colonoscope (11.5 mm diameter); and improved stricture ulceration score using SES-CD or DBE-CD.
Number of participants with improvement in general health
General health improvement was measured by patient reported outcomes of Inflammatory Bowel Disease (IBD) Quality of Life Questionnaire. The minimum and maximum values are 32 and 224 points respectively, and higher scores mean a better outcome.
Number of Participants with surgery
Number of Participants with surgery during follow-up included patients undergoing any surgery for endoscopic dilatation and stricture resection.
Number of participants with treatment success at week 104
Success at week 104 was defined in the same way as in week 52.
Degree of HBI reduction (Clinical response)
Clinical response was defined as HBI reduce at least three points
Reduction in CRP and FC levels (Biochemical ease)
Fecal calprotectin (FC) level ≤ 200 μg/g and/or CRP≤5 mg/L, or decrease ≥ 50%, compared to the baseline significant.
UST drug concentration
Measurements of UST drug concentration and antibody concentration, and their relationship with improvement of inflammation or imaging (CT enterography, bowel ultrasound, and endoscopy).
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Safety outcomes included the number of drug-related adverse events, infections, and disease-related hospitalizations per 100 patients per year. Adverse events were categorized as: possibly related, probably related, and not related to UST. Infections were classified as: 1) mild: infections that did not require medication; 2) moderate: infection treated with oral antibiotics or antiviral drugs; (3) Severe: infection requiring hospitalization or treatment with intravenous antibiotics or antiviral drugs.
Click on the lead sponsor to view all of their trials.
Second Affiliated Hospital, School of Medicine, Zhejiang University
Lead sponsor
Sixth Affiliated Hospital, Sun Yat-sen University
Collaborator
Second Affiliated Hospital of Soochow University
Collaborator
Chongqing Renji Hospital, University of Chinese Academy of Sciences
Collaborator
The First Affiliated Hospital of Zhejiang Chinese Medical University
Collaborator
Seventh Medical Center of PLA Army General Hospital
Collaborator
First People's Hospital of Hangzhou
Collaborator
Yangzhou University
Collaborator
Xian-Janssen Pharmaceutical Ltd.
Collaborator
