Extraintestinal Manifestations and Cytomegalovirus Reactivation Are Predictors of Difficult-To-Treat in Ulcerative Colitis

Q: What clinical outcomes does the study focus on in ulcerative colitis?

The study focuses on refractory ulcerative colitis patterns, including steroid dependence, steroid refractoriness, and difficult-to-treat (D-to-T) cases that do not respond to advanced therapies.

Q: How were patients grouped for analysis?

Patients with ulcerative colitis were classified into four groups: steroid-naive, steroid-free, steroid-dependent, and steroid-refractory. D-to-T cases were identified within the steroid-dependent and steroid-refractory groups.

Sep 30, 2026

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Ulcerative colitis remains difficult to manage when patients develop steroid dependence, steroid refractoriness, or difficult-to-treat (D-to-T) disease unresponsive to advanced therapies. A retrospective single-center analysis evaluated 216 UC patients (2017–2023), stratified into steroid-naive, steroid-free, steroid-dependent, and steroid-refractory groups. Extraintestinal manifestations (EIMs) and cytomegalovirus (CMV) reactivation differed significantly among groups, and multivariable models identified EIM and CMV reactivation as independent predictors across steroid-related categories and D-to-T status.

LanguageEnglish

CategoryHealthcare

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Pages11

Reading Time28 min

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Abstract

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Inflammatory Intestinal Diseases Research Article Inflamm Intest Dis 2026;11:18–28 DOI: 10. 1159/000549366 Received: August 14, 2025 Accepted: October 16, 2025 Published online: November 27, 2025 Extraintestinal Manifestations and Cytomegalovirus Reactivation Are Predictors of Difficult-To-Treat in Ulcerative Colitis Kotaro Akita a Mayuko Erataa Yoshihiro Yokoyama a Yuta Shimomoria Tomoe Kazama a Hiroki Kurumib Masanori Nojima c Hiroshi Nakasea aDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan; bDivision of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, Tottori University Faculty of Medicine, Tottori, Japan; cCenter for Translational Research, The Institute of Medical Science Hospital, The University of Tokyo, Minato-ku, Japan Keywords Ulcerative colitis · Steroid · Steroid dependence · Refractory · Difficult-to-treat · Extraintestinal manifestations · Cytomegalovirus Abstract Introduction: Ulcerative colitis (UC) is a diffuse, nonspecific inflammatory disease of unknown etiology. Although corticosteroids are essential for inducing remission in moderate to severe UC, steroid dependence and refractoriness remain significant clinical obstacles. Predicting which patients will develop steroid dependence or refractoriness remains challenging. Furthermore, difficult-to-treat (D-to-T) cases – those unresponsive to advanced therapies – have emerged as additional therapeutic concerns. This study aimed to identify factors associated with refractory UC, including steroid-dependent, steroid-refractory, and D-to-T presentations. Methods: A total of 216 patients with UC who received treatment at Sapporo Medical University Hospital between April 2017 and December 2023 were retrospectively analyzed. Patients were classified into four groups: steroidnaive (SN), steroid-free (SF), steroid-dependent (SD), and steroid-refractory (SR). D-to-T cases were identified within the SD and SR groups. Patient background characteristics were obtained from electronic medical records. Variables [karger@karger.com](karger@karger.com)[ ](karger@karger.com)[www.karger.com/iid](www.karger.com/iid) © 2025 The Author(s) . Published by S. Karger AG, Basel This article is licensed under the Creative Commons AttributionNonCommercial 4.0 International License (CC BY-NC) ([https://](https://)[ ](https://)[karger.com/Services/OpenAccessLicense](karger.com/Services/OpenAccessLicense)). Usage and distribution for commercial purposes requires written permission. analyzed included sex, age of onset, disease duration, alcohol consumption, smoking status, disease phenotype, extraintestinal manifestations (EIMs), and cytomegalovirus (CMV) and Clostridioides difficile infection status. Results: Significant differences were observed in the prevalence of EIM and CMV reactivation across the four groups (p < 0.001 for EIM; p < 0.001 for CMV). The prevalence of EIM was significantly higher in the SR group compared with the SN group (45.5% vs. 7.7%, p = 0.002) and the SF group (45.5% vs. 4.5%, p < 0.001). CMV reactivation was more frequent in the SR group than in the SN group (36.4% vs. 1.3%, p < 0.001) and the SF group (36.4% vs. 4.5%, p < 0.004). Multivariable analysis revealed that, in comparison with the SN group, the SD group was independently associated with EIM (odds ratio [OR] = 4.59, 95% confidence interval [CI]: 1.35–15.6) and CMVreactivation (OR = 12.5, 95% CI: 1.31–119). Compared to the SF group, the SD group was associated with EIM (OR = 5.71, 95% CI: 1.44–22.7). The SR group was independently associated with EIM (OR = 12.8, 95% CI: 2.51–64.9) and CMVreactivation (OR = 65.1, 95% CI: 4.39–964) compared to the SN group. Compared to the SF group, the SR group was associated with EIM (OR = 16.4, 95% CI: 2.95–90.8) and CMVreactivation (OR = 17.0, 95% CI: 2.03–142). There are also significant associations between D-t

FAQs

What clinical outcomes does the study focus on in ulcerative colitis?

The study focuses on refractory ulcerative colitis patterns, including steroid dependence, steroid refractoriness, and difficult-to-treat (D-to-T) cases that do not respond to advanced therapies.

How were patients grouped for analysis?

Patients with ulcerative colitis were classified into four groups: steroid-naive, steroid-free, steroid-dependent, and steroid-refractory. D-to-T cases were identified within the steroid-dependent and steroid-refractory groups.

Which factors were found to predict difficult-to-treat disease?

Extraintestinal manifestations (EIMs) and cytomegalovirus (CMV) reactivation were significantly associated with steroid dependence, steroid refractoriness, and resistance to biologic and molecular-targeted therapies, including associations with D-to-T status.

Sep 30, 2026

Uploaded by anakgang17