Abstract Background Corticosteroid (CS) therapy has traditionally played a crucial role as a bridge to advanced therapy (AT) in ulcerative colitis (UC) management. Recent availability of carotegrast methyl and oral budesonide has expanded treatment options before AT initiation, necessitating re-evaluation of CS use strategies. We previously reported that cumulative CS dose affects primary non-response (PNR) to initial AT. This study investigated the impact of CS dose, frequency, and administration patterns on subsequent treatment outcomes, including difficult-to-treat (D2T) UC. Methods We retrospectively analysed UC patients diagnosed after January 2010 with detailed CS treatment data available. We examined CS usage before the first AT (cumulative dose, frequency, duration, administration pattern) and assessed treatment response (PNR, loss of response LOR) and long-term outcomes. D2T UC was defined according to the IOIBD consensus criteria as failure of agents with two or more different mechanisms of action, plus surgical cases. Multivariate logistic regression identified risk factors for PNR and refractory disease. Results We analysed 98 UC patients (Table 1). Median age at onset was 41 years, at AT initiation 45 years. Mean cumulative CS dose was 1,655 mg, mean CS courses 1.5 (range 1-6). AT breakdown: infliximab/adalimumab/golimumab/vedolizumab/ustekinumab/upadacitinib/tofacitinib/filgotinib = 37/20/15/15/7/2/1/1. During mean follow-up of 626.3 days, PNR occurred in 24 patients (24.5%) and LOR in 21 (21.4%). Multivariate analysis (Figure 1) identified age ≥60 years at onset as the only significant risk factor for PNR (OR 5.5, 95% CI 1.49-20.3, p = 0.01), while cumulative CS ≥ 3,000 mg and ≥2 CS courses showed trends toward association (both p = 0.06). D2T UC occurred in 8 patients (8.2%) and surgery in 7 (7.1%), totalling 15 refractory cases (15.3%) with no overlap. For refractory disease, multivariate analysis identified cumulative CS ≥ 3,000 mg (OR 4.4, 95% CI 1.06-17.8, p = 0.04) and age ≥60 years at onset (OR 10.3, 95% CI 2.68-39.3, p 0.001) as independent risk factors (Figure 1). Conclusion Elderly-onset UC (≥60 years) requires careful attention due to poor treatment response. Prolonged CS therapy appears to adversely affect not only PNR but also overall long-term treatment outcomes. Cumulative CS dose ≥3,000 mg increases the risk of refractory disease 4.35-fold. These findings suggest that early transition to AT should be considered in elderly-onset patients, and cumulative CS dose of 3,000 mg may serve as a useful threshold for treatment strategy modification, potentially contributing to individualised UC management. References: 1. Parigi TL, Iacucci M, Ghosh S, et al. Difficult-to-treat inflammatory bowel disease: results from an international consensus meeting. Lancet Gastroenterol Hepatol. 2023;8(9):853-859. 2. Matsuoka K, Kobayashi T, Kakuta Y, et al. Factors associated with difficult-to-treat ulcerative colitis: analysis of a Japanese claims database. Intest Res. Published online April 25, 2025. 3. Turner D, Ricciuto A, Lewis A, et al. STRIDE-II: an update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology. 2021;160(5):1570-1583. 4. Yokoo T, Yoshikawa S, Masuda T, et al. Impact of cumulative corticosteroid dose on primary non-response to advanced therapy in ulcerative colitis. Presented at: 16th Congress of Japanese Society for Inflammatory Bowel Disease; August 22-23, 2025; Sapporo, Japan. Conflict of interest: Dr. Yokoo, Takashi: Personal Fees: Honoraria for lectures from AbbVie, Bristol Myers Squibb, Chugai, EA Pharma, Gilead Sciences, Johnson & Johnson, Kaken, Kyorin, Mitsubishi Tanabe Pharma, Mochida, and Takeda (past 36 months). Yoshikawa, Shyuusaku: No conflict of interest Masuda, Tsutomu: No conflict of interest Terauchi, Seiji: No conflict of interest Uchida, Hideki: No conflict of interest Nakao, Takeshi: No conflict of interest Inagaki, Mizumi: No conflict of interest Tani, Takafumi: No conflict of interest Okamoto, Kouhei: No conflict of interest Shibata, Yusuke: No conflict of interest Inatsugi, Naoki: No conflict of interest
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