Efficacy and safety in the short-to-intermediate term of advanced combination therapy with upadacitinib for refractory Crohn’s disease: real-world evidence from eastern China

Aims To evaluate the real-world efficacy and safety of advanced combination therapy with upadacitinib (ACT-U) in East Asian patients with refractory Crohn’s disease (CD). Methods This single-center, retrospective, observational study conducted at Yancheng No.1 People’s Hospital (Jiangsu, China) evaluated the efficacy and safety of ACT-U in 26 patients with refractory CD. Participants received ACT-U (upadacitinib + biologics) following inadequate response to ≥1 biologic. Clinical, endoscopic, and biochemical outcomes were assessed at baseline and posttreatment. Safety profiles were monitored throughout the follow-up period to evaluate the risk of adverse events. Results Patients (median age 27.5 years [IQR, 23.3–32.0], median disease duration 4.0 years [3.0–6.0]) received ACT-U for a median of 14.5 weeks [11.0–18.8]. Median HBI decreased from 7 [6–8] to 2 [2–4] ( p < 0.01). All patients achieved clinical response (95% CI: 85.8, 100%), and 91.7% attained remission (95% CI: 73.0, 99.0%). Median SESCD decreased from 15 [13–17] to 1 [0–2], with ( p < 0.01). All patients achieved endoscopic improvement (95% CI: 85.8, 100%), 83.3% achieved remission (95% CI: 62.6, 95.3%), and 45.8% attained healing (95% CI, 25.6, 67.2%). Mild AEs occurred in 23.1% (95% CI, 9.0, 43.6%; acne, gastrointestinal disturbances, mild infections), including one transient semen discoloration case. No severe AEs or surgeries reported. Conclusion ACT-U aligned with the STRIDE-II goals, demonstrating accelerated attainment of short-to-intermediate term endpoints (per STRIDE-II recommendations). Despite limitations, including its retrospective design and small case series, we provide foundational real-world evidence supporting ACT-U as a well-tolerated and effective regimen for refractory CD in EAS patients. Further prospective studies are warranted to validate long-term outcomes, optimize combination strategies, and assess applicability across diverse frameworks.