Value of IUS in Predicting Vedolizumab Efficacy and Assessing Transmural Healing in Early Crohn's Disease: A Multicenter, Prospective Study

Official title

Value of Intestinal Ultrasound in Predicting Vedolizumab Response and Assessing Transmural Healing in Early Crohn's Disease: A Multicenter, Prospective Study

Overview

Crohn's disease(CD) is a chronic nonspecific inflammatory disease of the intestinal tract whose etiology is not yet fully understood,characterized by transmural inflammation , can present with serious complications such as intestinal obstruction, perforation, abdominal abscesses, and fistulae. In recent years, the incidence of CD has increased rapidly, causing a heavy social and economic burden. Currently, the main therapeutic drugs for CD include aminosalicylic acid preparations, glucocorticoids, immunosuppressants, and biological agents. With the development of medical technology, small molecule preparations have begun to be applied to moderate-to-severe Crohn's disease, providing new treatment options for patients with Crohn's disease. Vedolizumab, a humanized monoclonal antibody.the GEMINI study demonstrated its superior efficacy over placebo in inducing and maintaining clinical remission. And the VERSIFY study confirmed its advantage in achieving mucosal healing, with a transmural healing rate of 29.1% at week 52. Intestinal ultrasound is a noninvasive, reproducible, convenient, and inexpensive test that can greatly increase the frequency of assessing treatment response and speed up the clinical decision-making process.The 2019 ECCO-ESGAR guidelines recommend intestinal ultrasound for disease monitoring in patients with CD. Multiple studies have shown that most ultrasound markers normalize within 12 weeks of treatment initiation, and in particular, normalization of bowel wall thickness is highly correlated with clinical response at 12 weeks. There are no validated indicators to predict the efficacy of upadacitinib treatment in patients with moderate-to-severe CD in the currently available studies. Currently, there are no national or international studies in which intestinal ultrasound predicts the efficacy and assesses the transmural healing of vedolizumab therapy. Therefore, we propose for the first time that intestinal ultrasound be used as a method to predict the response to vedolizumab in early CD patients, with the aim of providing evidence to guide the development of individualized treatment plans.

Detailed description

Crohn's disease(CD) is a chronic nonspecific inflammatory disease of the intestinal tract whose etiology is not yet fully understood,characterized by transmural inflammation , can present with serious complications such as intestinal obstruction, perforation, abdominal abscesses, and fistulae. In recent years, the incidence of CD has increased rapidly, causing a heavy social and economic burden. Patients often experience prolonged, relapsing disease courses , with approximately 30% developing irreversible damage such as intestinal strictures or perforation at diagnosis due to delayed detection, resulting in substantial disease burden.Currently, the main therapeutic drugs for CD include aminosalicylic acid preparations, glucocorticoids, immunosuppressants, and biological agents. With the development of medical technology, biologics have begun to be applied to moderate-to-severe Crohn's disease, providing new treatment options for patients with Crohn's disease.However, subclinical inflammatory activity persists in some patients , and long-term use carries risks of secondary infections, malignancies, and loss of response. Therefore, accurately predicting treatment response to biologics and assessing transmural healing in early CD patients remains an urgent clinical challenge.

Vedolizumab, a humanized monoclonal antibody,specifically targets α4β7 integrin to block lymphocyte migration to gut mucosa, thereby suppressing local inflammation and improving CD symptoms.The phase 3 GEMINI trial by Sands BE et al. demonstrated vedolizumab's superiority over placebo in inducing and maintaining clinical remission. The VERSIFY study further confirmed its efficacy in achieving mucosal healing, with a 29.1% transmural healing rate at week 52 versus placebo . However, vedolizumab may increase infection risk, with common adverse effects including nasopharyngitis, headache, and arthralgia. Approximately 30% of patients exhibit primary non-response, highlighting the importance of early response identification and longitudinal monitoring Intestinal ultrasound is a noninvasive, reproducible, convenient, and inexpensive test that can greatly increase the frequency of assessing treatment response and speed up the clinical decision-making process.The 2019 ECCO-ESGAR guidelines recommend intestinal ultrasound for disease monitoring in patients with CD. Multiple studies have shown that most ultrasound markers normalize within 12 weeks of treatment initiation, and in particular, normalization of bowel wall thickness is highly correlated with clinical response at 12 weeks. There are no validated indicators to predict the efficacy of upadacitinib treatment in patients with moderate-to-severe CD in the currently available studies.

Currently, there are no national or international studies in which intestinal ultrasound predicts the efficacy and assesses the transmural healing of vedolizumab therapy. Therefore, we propose for the first time that intestinal ultrasound be used as a method to predict the response to vedolizumab in early CD patients, with the aim of providing evidence to guide the development of individualized treatment plans.

Primary outcome measures

• Bowel wall thickess(BWT) [Time frame: follow-up time of about 52 weeks]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years and ≤ 80 years;
• Early CD patients (disease duration ≤18 months, biologic-naïve and treatment-naïve for advanced therapies, without complications such as fistulas or strictures)
• Vedolizumab therapy is proposed to be applied within 1 month after baseline endoscopy and intestinal ultrasound,;
• No history of intestinal surgery;
• Clearly understand, voluntarily participate in the study, and sign an informed consent form.

Exclusion criteria

• Contraindications to vedolizumab: allergy, active tuberculosis or other active infections, moderate-to-severe heart failure (NYHA grade III/ IV), demyelinating lesions of the nervous system, live vaccination within the last 3 months, pregnancy and lactation;
• Patients with a history of extensive colectomy or recent proposed colectomy, history of colonic mucosal dysplasia;
• Hypersensitivity to the components of SonoVue contrast media.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 1 center

• The Third Xiangya Hospital of Central South University — Changsha

Identifiers

NCT: NCT07093294 · fu3tianli7

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗