Real-world efficacy and safety of upadacitinib in difficult-to-treat Crohn’s disease: a 24-week multicenter study from China

Background/Aims: Real-world evidence for upadacitinib use in strictly defined difficult-to-treat Crohn's disease (DTT-CD), particularly in Asian populations, remains limited. Herein, we aimed to evaluate the efficacy and safety of upadacitinib in Chinese patients with DTT-CD. Methods: This multicenter, bidirectional cohort study was conducted at 8 Chinese inflammatory bowel disease centers. Patients received upadacitinib 45 mg once daily for 12 weeks induction, followed by 15 mg daily for maintenance. The coprimary endpoints were clinical remission at week 12 and week 24. Results: Among the 151 DTT-CD patients enrolled, the clinical remission rates were 47.0% at week 12 and 62.9% at week 24, with endoscopic remission achieved in 28.1% of patients at week 24. Adverse events occurred in 42 (27.8%) during induction and in 33 (21.9%) during maintenance, with 3 serious events (venous thrombosis, perforation, and hemorrhage) reported during the maintenance phase. Notably, 2 male reproductive system-related adverse events were observed, including blue semen in 2 patients and a suspected case of paternal teratogenicity with fetal anomalies and pregnancy loss. The drug persistence at week 24 was 93.4%. Conclusions: Upadacitinib demonstrated robust efficacy in Chinese patients with DTT-CD, with a manageable safety profile and high treatment persistence.