Abstract Background Difficult-to-treat inflammatory bowel disease (D2T-IBD) has been defined by the IOIBD as a condition refractory to two or more advanced therapy (AT) with different mechanisms of action. However, the clinical characteristics and treatment persistence of D2T ulcerative colitis (UC) in Japanese patients remain unclear. This study aimed to compare the real-world outcomes of D2T and non-D2T UC in our institution. Methods We retrospectively analysed UC patients who initiated biologics or small-molecule therapy between January 2019 and December 2024. Patients were categorised into D2T and non-D2T groups. Treatment response was defined as follows: discontinuation within 3 months as ineffective, discontinuation between 3–12 months as partially effective, and continuation for ≥12 months as effective. Discontinuations due to adverse events were also recorded. Results A total of 155 treatment courses in 102 UC patients were analysed (D2T: 32, non-D2T: 87). Ineffectiveness was observed in 10/32 (31.3%) D2T courses and 13/87 (14.9%) non-D2T courses. Partial response was seen in 4/16 (25.0%) and 22/64 (34.4%) courses, respectively. Kaplan–Meier analysis showed no significant difference in treatment persistence between the two groups. In contrast, JAK inhibitors demonstrated significantly higher persistence than non-JAK therapy in the non-D2T group (P = 0.001). Since JAK inhibitors were more frequently used in the D2T group, this may have mitigated differences in overall persistence rates between the groups. Conclusion Approximately one-quarter of UC patients met the D2T criteria in real-world practice. Although ineffectiveness was more frequent in D2T cases, overall treatment persistence was comparable to that of non-D2T patients, possibly due to proactive use of JAK inhibitors in the D2T group. References: 1. Torres J, Chaparro M, Katsanos KH, et al. Defining difficult-to-treat inflammatory bowel disease: Consensus from the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD). J Crohns Colitis. 2021;15(12):1980–1990. 2. Harbord M, Eliakim R, Bettenworth D, et al. The IOIBD definitions of disease behaviour in ulcerative colitis and Crohn’s disease. J Crohns Colitis. 2016;10(12):1304–1308. Conflict of interest: Dr. Yamaguchi, Yoshiharu: No conflict of interest Tomita, Mayu: No conflict of interest Tashiro, Takashi: No conflict of interest Onishi, Kentaro: No conflict of interest Ono, Sstoshi: No conflict of interest Tanaka, HItoshi: No conflict of interest Kawamura, Tatsuya: No conflict of interest Adachi, Kazunori: No conflict of interest Ebi, Masahide: No conflict of interest Ogasawara, Naotaka: No conflict of interest Sasaki, Makoto: No conflict of interest Nakamura, Masanao: No conflict of interest
Yamaguchi et al. (Thu,) studied this question.