Overview
This is a prospective, single-center, observational study aimed at evaluating the efficacy and safety of guselkumab in patients with moderate to severe Crohn's disease (CD) who have previously failed or were intolerant to ustekinumab therapy. The study plans to enroll approximately 60 participants aged 18-75 years. Participants will receive guselkumab treatment following a defined induction and maintenance regimen over a total observation period of 52 weeks. The primary endpoint is the proportion of patients achieving clinical remission at Week 52. Secondary endpoints include clinical response, endoscopic improvement, biomarker normalization, quality of life assessment, and safety monitoring.
Description
Crohn's disease is a chronic, progressive, and disabling inflammatory bowel disease. Ustekinumab, a monoclonal antibody targeting the p40 subunit of IL-12/23, is an established treatment option. However, a significant proportion of patients experience primary non-response, secondary loss of response, or intolerance. Guselkumab is a fully human monoclonal antibody that selectively targets the p19 subunit of IL-23, a key cytokine in the Th17-mediated inflammatory pathway in CD. While guselkumab has demonstrated efficacy in biologic-naïve or TNF-antagonist failed CD patients, real-world prospective data in ustekinumab-experienced patients are limited. This study aims to fill this evidence gap by providing prospective observational data on the effectiveness and safety of guselkumab in this specific patient population.
Eligibility
Inclusion Criteria:
- Age 18-75 years.
- Diagnosis of Crohn's disease for at least 3 months.
- Moderate to severe disease activity (CDAI 220-450).
- Previous treatment with at least one standard dose of ustekinumab with documented:
- Primary non-response, or Secondary loss of response, or Intolerance leading to discontinuation.
- Willing and able to comply with all study visits and procedures.
Exclusion Criteria:
- Previous exposure to any anti-IL-23p19 therapy (including guselkumab).
- Active intestinal infection, unremoved stenotic lesions with obstructive symptoms, short bowel syndrome, stoma, or recent abdominal abscess (\<8 weeks).
- History of malignancy (except certain skin cancers), active tuberculosis, or severe opportunistic infection.
- Pregnancy, lactation, or planned pregnancy during the study period.
