Guselkumab plus a JAK inhibitor for difficult-to-treat inflammatory bowel disease

Efficacy and Safety of Guselkumab (GUS) With JAK Inhibitors in Patients With Difficult-To-Treat IBD

This project will try guselkumab together with a JAK inhibitor in people aged 14–80 whose moderate-to-severe inflammatory bowel disease has not responded to multiple other treatments.

Quick facts

• Study type: Observational
• Enrollment: 80 (estimated)
• Ages: 14 Years to 80 Years
• Sex: All
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (Academic / other)
• Drugs / interventions: guselkumab, upadacitinib, tofacitinib
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT07487311 on ClinicalTrials.gov

What this trial studies

This is a single-center prospective observational cohort enrolling patients aged 14–80 with moderate-to-severe refractory IBD who have failed multiple biologics or meet surgical/perianal criteria. Participants treated with guselkumab combined with a JAK inhibitor (for example upadacitinib or tofacitinib) will be followed for safety and clinical outcomes, including CDAI, SES-CD, and modified Mayo scores. The study will track prior treatment history, surgical status, adverse events, and clinical response and remission rates over scheduled follow-up visits. Results are intended to provide real-world evidence on the tolerability and potential effectiveness of combining an IL-23 blocker with JAK inhibition in a hard-to-treat population.

Who should consider this trial

Good fit: Ideal candidates are people aged 14–80 with confirmed moderate-to-severe IBD who meet criteria for refractory disease (including failure of at least two biologics or recurrent surgery/complex perianal disease) and can give informed consent.

Not a fit: Patients with active infections, abscesses, malignancy, severe cardiopulmonary disease, pregnancy or lactation, history of thromboembolism, severe organ insufficiency, severe cytopenia, or prior intolerance to JAK or IL-23 inhibitors are unlikely to benefit or are excluded.

Why it matters

Potential benefit: If successful, the combination could bring remission and improved quality of life to patients with refractory IBD who have exhausted standard options.

How similar studies have performed: Individual IL-23 antagonists and JAK inhibitors have shown benefit in IBD, but combining guselkumab with JAK inhibitors is largely untested and represents a novel, experimental approach.

Eligibility criteria

Inclusion Criteria:

* Age 14-80 years with confirmed diagnosis of IBD;
* Meeting the definition of refractory IBD (1. Failure of at least two biologics with different mechanisms of action; 2. Crohn's disease with recurrence after two or more intestinal resections; 3. Complex perianal disease despite treatments 1 and 2);

  * Moderate to severe active IBD (CD: CDAI 220-450, SES-CD ≥6 or isolated ileal disease ≥4; UC: Baseline modified Mayo score (mMayo) of 4-9, rectal bleeding score ≥1, endoscopic score ≥2);
  * Signed informed consent.

Exclusion Criteria:

* Active infection, abscess, malignancy, severe cardiopulmonary disease, pregnancy or lactation;

  * History of thromboembolism, severe hepatic or renal insufficiency, severe cytopenia;
  * Prior intolerance to JAK inhibitors or IL-23 inhibitors.

Where this trial is running

Hangzhou, Zhejiang

• Center of Inflammatory Bowel Disease, Department of Gastroenterology, the Second Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Shurong Hu, PhD

Conditions Inflamatory Bowel Disease