IUS Predicts Guselkumab Efficacy in Patients With Moderate to Severe Crohn's Disease：a Prospective Study

Recruiting

• Conditions: Crohn's Disease; Guselkumab; Intestinal Ultrasound; Predictor

• Registration Number: NCT07034664
• Lead Sponsor: The Third Xiangya Hospital of Central South University

Brief Summary

Crohn's disease (CD) is a chronic non-specific intestinal inflammatory disease with incompletely clarified etiology, which can involve multiple organs and systems , and is prone to severe complications such as intestinal obstruction, perforation, and fistula.Currently, the main therapeutic drugs for CD include aminosalicylates, glucocorticoids, immunosuppressants, biological agents, etc. With the development of medical technology, biological agents have begun to be applied to moderate-to-severe Crohn's disease, providing new treatment options for patients with moderate-to-severe Crohn's disease.

Guselkumab is a selective inhibitor of the interleukin-23 (IL-23) p19 subunit.The GALAXI2 and GALAXI3 studies demonstrated that guselkumab can better achieve the therapeutic goal of mucosal healing. The clinical remission rates of guselkumab at week 12 were 47.1% and 47.1%, respectively, and the endoscopic response rates were 37.7% and 36.2%, respectively .

Intestinal ultrasound lUsnoninvasive, 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 intestinalultrasound for disease monitoring in patients with CD. There are no validated indicators to predict the efficacy of guselkumab treatment in patients with moderate-to-severe CD in the currently available studies.

Currently, there are no national orinternational studies in which intestinal ultrasound predicts the efficacy of guselkumab therapy. Therefore, we propose for the first time that intestinal ultrasound be used as a method to predict the response to guselkumab in CD patients, with the aiproviding evidence to guide the development of individualized treatment plans.

Detailed Description

Crohn's disease (CD) is a chronic non-specific intestinal inflammatory disease with incompletely clarified etiology, which can involve multiple organs and systems , and is prone to severe complications such as intestinal obstruction, perforation, and fistula. In recent years, the incidence of CD in China has rapidly increased and shown a younger trend . Patients often face the dilemma of prolonged course and repeated attacks. Among them, moderate-to-severe patients are confronted with problems such as complex condition and large individual differences in treatment effects, causing a heavy social and economic burden . Currently, the main therapeutic drugs for CD include aminosalicylates, glucocorticoids, immunosuppressants, biological agents, etc. With the development of medical technology, biological agents have begun to be applied to moderate-to-severe Crohn's disease, providing new treatment options for patients with moderate-to-severe Crohn's disease. The application of biological agents has changed the course of CD, but such drugs need to be used for a long time, and there are risks such as secondary infection, tumor, and loss of response. Therefore, effectively predicting the efficacy of biological agents in patients with moderate-to-severe CD is an urgent clinical problem to be solved.

Guselkumab is a selective inhibitor of the interleukin-23 (IL-23) p19 subunit,which inhibits the IL-23-mediated inflammatory signaling pathway, effectively reducing intestinal inflammatory responses and alleviating symptoms of Crohn's disease. In the phase 3 GRAVITI study by Hart A et al. on guselkumab for moderate-to-severe active Crohn's disease, the results of this multicenter, double-blind induction therapy trial showed that the clinical remission rate and endoscopic response rate of guselkumab were significantly superior to those of placebo . The GALAXI2 and GALAXI3 studies demonstrated that guselkumab can better achieve the therapeutic goal of mucosal healing. The clinical remission rates of guselkumab at week 12 were 47.1% and 47.1%, respectively, and the endoscopic response rates were 37.7% and 36.2%, respectively . However, the use of guselkumab may increase the risk of infection in patients, leading to adverse reactions such as nasopharyngitis and upper respiratory tract infections. Other adverse reactions include headache, arthralgia, diarrhea, etc. Meanwhile, some patients still exhibit poor efficacy or no response to this drug. Therefore, early identification of drug responders, monitoring of long-term efficacy, and real-time monitoring of the mucosal healing process are of great importance. This has significant practical implications for guiding the formulation of individualized treatment plans and optimizing clinical decisions.

Intestinal ultrasound (IUS) 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 guselkumab 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 of guselkumab therapy. Therefore, we propose for the first time that intestinal ultrasound be used as a method to predict the response to guselkumab in CD patients, with the aim of providing evidence to guide the development of individualized treatment plans.

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-15
• Study First Submitted QC: 2025-06-15
• Last Update Submitted: 2025-06-15
• Study Start: 2025-06-16
• Study First Posted: 2025-06-24
• Last Update Posted: 2025-06-24
• Primary Completion: 2027-07-30
• Study Completion: 2027-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

Age ≥ 18 years and ≤ 80 years;

• Patients with newly diagnosed or relapsed moderate to severe Crohn's disease;
• Guselkumab therapy is proposed to be applied within 1 month after baseline endoscopy and intestinal ultrasound;
• No history of abdominal surgery;
• Clearly understand, voluntarily participate in the study, and sign an informed consent form.

Exclusion Criteria

• Contraindications to Guselkumab: allergy, active tuberculosis or other active infections, and comorbidities such as severe liver dysfunction;
• Patients with a history of extensive colectomy or recent proposed colectomy, history of colonic mucosal dysplasia;
• Hypersensitivity to the components of SonoVue contrast media.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Bowel wall thickness(BWT)	follow-up time of about 56weeks	BWT is measured by intestinal ultrasound. BWT≤3mm means that CD is in quiescent, \>3mm means CD is active

Trial Locations

Locations (1)

The Third Xiangya Hospital of Central South University; 🇨🇳 Changsha, Hunan, China