Patients with refractory inflammatory bowel disease (IBD) show inadequate response to conventional biologics and small molecule drugs, with persistently active disease that severely impacts quality of life and long-term prognosis. Current treatment options are limited, and the substantial disease heterogeneity makes traditional randomized controlled trials difficult to implement in this population. This study aims to explore the efficacy and safety of guselkumab (GUS) with JAK inhibitors (such as upadacitinib/tofacitinib) in this patient population, providing novel therapeutic strategies for clinical practice.

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.

Moderate to severe active Inflammatory bowel disease