P0786 Real-world effectiveness and safety of upadacitinib in difficult-to-treat Crohn’s Disease: A national multicenter study from China

Abstract Background Difficult-to-treat Crohn’s disease (DTT-CD) accounts for approximately one-quarter of the CD population. The management of DTT-CD poses a significant clinical challenge. Upadacitinib(UPA) is considered a potent small-molecule drug; however, clinical studies on its efficacy and safety in DTT-CD remain scarce. Methods We conducted an ambidirectional, national, multicenter study across eight Chinese IBD centers from January 2023 to January 2025. Patients meeting IOIBD criteria for DTT-CD were included. The treatment regimen consisted of an induction phase with UPA 45 mg once daily for 12 weeks, followed by a maintenance phase of 15 mg once daily. Efficacy and safety were assessed at week 12 and week 24. The primary endpoint was the clinical remission rate at week 24. Secondary endpoints included the endoscopic remission rate at week 24, as well as clinical remission and response rates at week 12, and clinical response and endoscopic response rates at week 24. Safety events were evaluated at both week 12 and week 24. Results A total of 151 patients were enrolled (Table 1). Endoscopic evaluation was completed in 89 patients at week 24. The clinical remission rate at week 24 was 63.2%, and the endoscopic remission rate was 28.9%. Additionally, at week 24, 82.9% of patients achieved clinical response, and 42.2% achieved endoscopic response. A total of 42 adverse events (AEs) were reported by week 12, with no serious adverse events (SAEs) observed (Table 2). By week 24, 32 AEs had occurred, including acne (n = 10), anemia (n = 7), fever (n = 3), blue semen (n = 2, male patients), fatigue (n = 1), herpes zoster (n = 1), vaginitis (n = 1), hematuria (n = 1), rash (n = 1), leukopenia (n = 1), and mild elevation of creatine kinase (n = 1). SAEs included lower limb venous thrombosis (n = 1), intestinal perforation (n = 1), and massive hemorrhage (n = 1). Notably, blue semen was reported as an AE for the first time. Compared with the AEs documented at week 12, more AEs were reported at week 12, whereas SAEs emerged by week 24. By week 24, a total of 9 patients had discontinued UPA. Among them, 3 patients with serious AEs discontinued treatment and were hospitalized. Other reasons for discontinuation included: two patients due to fever, one due to anemia, and three due to lack of endoscopic response. Conclusion This study represents the largest cohort of Asian patients with DTT-CD to date. The findings demonstrate that UPA provides robust and sustained clinical and endoscopic efficacy in a real-world Chinese cohort with DTT-CD, along with a manageable safety profile. Additionally, several novel adverse events were observed in this real-world study. These findings support the use of UPA as a valuable therapeutic option in this challenging population. References: 1. Parigi TL, D’Amico F, Abreu MT, et al. Difficult-to-treat inflammatory bowel disease: results from an international consensus meeting. Lancet Gastroenterol Hepatol. 2023;8(9):853-859. doi:10.1016/S2468-1253(23)00154-1 2. Parigi TL, Massimino L, Carini A, et al. Prevalence, Characteristics, Management, and Outcomes of Difficult-to-Treat Inflammatory Bowel Disease. J Crohns Colitis. 2025;19(3):jjae145. doi:10.1093/ecco-jcc/jjae145 3. Bezzio C, Franchellucci G, Savarino EV, et al. Upadacitinib in Patients With Difficult-to-Treat Crohn’s Disease. Crohns Colitis 360. 2024;6(4):otae060. Published 2024 Oct 24. doi:10.1093/crocol/otae060 4. Loftus EV Jr, Panés J, Lacerda AP, et al. Upadacitinib Induction and Maintenance Therapy for Crohn’s Disease. N Engl J Med. 2023;388(21):1966-1980. doi:10.1056/NEJMoa2212728 Conflict of interest: Zhang, Zile: No conflict of interest Zhang, Shuowen: No conflict of interest Ge, Wensong: No conflict of interest Li, Yue: No conflict of interest Ruidong, Chen: No conflict of interest Tang, Wen: No conflict of interest Qunying, Wang: No conflict of interest Fan, Yihong: No conflict of interest Zhou, Linyan: No conflict of interest Tian, Feng: No conflict of interest Chen, Chunxiao: No conflict of interest Gu, Yubei: No conflict of interest Zou, Duowu: No conflict of interest