Effectiveness of ustekinumab in Crohn's disease across intestinal locations: spotlight on isolated small intestinal involvement.

BACKGROUND

Small intestinal-predominant Crohn's disease (CD) exhibits distinct therapeutic patterns and is characterized by increased biological use and intestinal resection rates. However, systematic evaluations of the objective response of ustekinumab (UST), particularly related to disease location, are limited.

OBJECTIVES

To compare the therapeutic efficacy of UST between small intestinal CD (SICD) and non-small intestinal CD (NSICD).

DESIGN

A prospective observational cohort study.

METHODS

Demographic and clinical characteristics were collected at baseline and 52-week follow-up, assessments including endoscopy, imaging, ultrasonography (US), histopathology, fecal calprotectin (FCP), C-reactive protein (CRP), and hemoglobin results. Patients with isolated ileal involvement (Montreal classification L1) were classified as having SICD, while NSICD was defined by L2 and L3. Primary outcome was objective remission, defined by meeting one of the following: (1) endoscopic remission (ER): Simple endoscopic score for CD (SES-CD) ⩽ 2. (2) US remission: normal bowel wall thickness and absence of Doppler signals or detectable complications, or (3) radiological remission: complete resolution of inflammatory features. Secondary outcomes included (1) mucosal healing (MH): absence of ulcerations. (2) transmural healing (TH): complete healing of all intestinal wall layers, and (3) biochemical remission: FCP/CRP normalization, (4) objective response: a clear improvement from baseline, and (5) endoscopic response: SES-CD ⩽ 4.

RESULTS

This study included 331 patients with CD (SICD 36.9%, NSICD 63.1%). Of these, 309 completed a 52-week follow-up. Objective remission, MH, and TH were achieved by 32.7%, 25.6%, and 13.6% of patients, respectively. Biochemical remission occurred in 41.5% (FCP) and 35.2% (CRP). Objective and endoscopic responses were observed in 70.2% and 42.1% of patients, respectively. Objective remission was achieved in 54/116 patients (46.6%) in the SICD group and 47/193 (24.4%) in the NSICD group. Regression analyses and propensity score matching showed significantly higher rates of objective remission, MH, and endoscopic response in the SICD group.

CONCLUSION

Disease location influenced UST treatment outcomes, with SICD showing higher rates of objective remission, MH, and endoscopic response than NSICD.