Two-Drug cocktail aims to tame stubborn Crohn's disease

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Aged 18 to 65 years. * Patients with a confirmed diagnosis of Crohn's disease according to the European Crohn's and Colitis Organisation (ECCO) criteria. * Patients with prior failure, loss of response, intolerance, or contraindication to anti-TNF therapy, who subsequently had inadequate response to ustekinumab or upadacitinib monotherapy between July 1, 2023 and May 31, 2025. * Active Crohn's disease defined by Harvey-Bradshaw Index (HBI) \>4, or endoscopic disease activity with at least one segment having an SES-CD ulcer subscore ≥2. Postoperative endoscopic recurrence was defined as modified Rutgeerts score ≥i2b. For patients in whom the small bowel anastomosis could not be reached endoscopically, disease activity was assessed by the treating physician based on clinical symptoms, elevated inflammatory markers, and imaging findings. * Patients who required dose reduction during full-dose upadacitinib treatment because of adverse events, or who had persistent clinical symptoms, elevated C-reactive protein, active endoscopic disease, postoperative recurrence, or active disease on imaging despite upadacitinib treatment. * Patients with inadequate response or loss of response to ustekinumab treatment, defined by persistent clinical symptoms, elevated C-reactive protein, active endoscopic disease, postoperative recurrence, imaging evidence of active disease, or recurrence after initial response during maintenance therapy. * Availability of inflammatory markers and imaging results within 3 months before initiation of combination therapy. Exclusion Criteria: * Patients receiving upadacitinib in combination with biologics other than ustekinumab. * Patients receiving full-dose upadacitinib 45 mg/day in combination with ustekinumab. * Patients with contraindications to upadacitinib, including hypersensitivity to the active substance or excipients, active tuberculosis or severe infection, malignancy, thromboembolic events, or severe hepatic impairment. * Patients with severe infection, malignancy, pregnancy, or lactation. * Patients with severe intestinal stricture, perforation, or intra-abdominal abscess that might require surgery and interruption of drug therapy during the study period. * Patients considered unsuitable for the above treatment by the treating physician. * Patients with incomplete data, inability to complete follow-up, or loss to follow-up.