Background & Aims: Isolated small bowel Crohn's disease (CD) is defined by involvement of the ileum, jejunum, or extensive small intestinal segments in the absence of colonic disease. This phenotype presents a therapeutic challenge, as biologic agents demonstrate reduced efficacy in this subgroup. Data on the use of upadacitinib specifically for isolated small bowel CD remain limited. This study aimed to evaluate the efficacy of upadacitinib in patients with this phenotype using the International Bowel Ultrasound Segment Activity Score (IBUS-SAS).

Methods: A retrospective cohort study including individuals with active Crohn's disease (CD) who received 12-week induction therapy with upadacitinib (45 mg/day) was conducted. Based on whether the disease involved the small bowel, individuals were categorized into an isolated small bowel CD group and a non-small bowel CD group. The primary endpoint was the change in the International Bowel Ultrasound Segment Activity Score (IBUS-SAS) from baseline to week 12. Secondary endpoints at week 12 included radiographic response (defined as a>25% or>2.0 mm reduction in bowel wall thickness [BWT] from baseline, or a>1.0 mm reduction in BWT from baseline accompanied by a decreased Color Doppler Signal grade), change in clinical activity as measured by the Crohn's Disease Activity Index (CDAI) from baseline, and changes in laboratory parameters (C-reactive protein, erythrocyte sedimentation rate). Statistical analyses included between-group comparisons, within-group comparison and logistic regression to identify predictors of radiographic response.

Inclusion Criteria:

• confirmed diagnosis of Crohn's disease (CD) based on the 2023 Chinese clinical practice guidelines (Guangzhou);
• initiated upadacitinib treatment (45 mg once daily) and completed at least 12 weeks of follow-up;
• underwent intestinal ultrasound examinations both before treatment initiation and at week 12

Exclusion Criteria:

• age <18 years;
• concomitant use of other CD medications during upadacitinib treatment, including glucocorticoids, mesalazine, immunosuppressants, or biologics;
• undergoing surgical intervention during the upadacitinib treatment period
• history of other gastrointestinal diseases (e.g., ulcerative colitis, intestinal tuberculosis);
• incomplete clinical data.

This retrospective case-control study consecutively enrolled individuals with Crohn's disease who initiated upadacitinib treatment at The Sixth Affiliated Hospital of Sun Yat-sen University between March 2023 and December 2024.