ORIGINAL RESEARCH article
Front. Med.
Sec. Gastroenterology
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
Zhen-yu YE 1,2
Yang Huang 3
Ya-nan Wang 4,2
Xiang-su Li 2
Xin Wang 2
Xu-dong Wu 2
1. School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
2. Department of Gastroenterology, Yancheng No 1 People's Hospital, Yancheng, China
3. Department of Gastroenterology, Zhenjiang First People's Hospital, Zhenjiang, China
4. Department of Gastroenterology, Yancheng Clinical College, Xuzhou Medical University, Xuzhou, China
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Abstract
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, P.R. 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. Conclusions: 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.
Summary
Keywords
adverse drug reactions, Biological Therapy, Crohn's disease, IBD CLINICAL, Upadacitinib
Received
15 October 2025
Accepted
02 February 2026
Copyright
© 2026 YE, Huang, Wang, Li, Wang and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Xu-dong Wu
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