Introduction: Systemic corticosteroids remain widely used in ulcerative colitis (UC), yet approximately half of initial responders relapse during tapering or soon after discontinuation (steroid dependency). Understanding patients at risk of steroid dependency may inform individualized treatment strategies. Here, we explore factors associated with steroid dependency using conventional regression analysis and an exploratory artificial neural network approach. Methods: Consecutive patients with UC who received their first course of systemic corticosteroids from May 2012 to March 2020 were retrospectively screened, and those who responded to corticosteroids at day 30 were enrolled from four institutions. Factors associated with steroid dependency were assessed by multivariable logistic regression and a self-organizing map (SOM), an unsupervised neural network. Steroid dependency was defined as clinical relapse during tapering or within 3 months after completion of corticosteroids. Results: A total of 107 patients who showed a clinical response at day 30 were analyzed. Thirty-three (30.8%) patients developed steroid dependency. In the multivariable logistic analysis, extensive colitis, initial dose of prednisolone, and two-item patient-reported outcome score at day 30 were independently associated with steroid dependency. In the SOM analysis, patients were categorized into 8 clusters with variable rates of steroid dependency, indicating heterogeneous multidimensional clinical patterns beyond those captured by conventional regression analysis. Conclusion: By combining an unsupervised SOM with conventional logistic regression, our study provided an exploratory visualization of multidimensional clinical patterns associated with steroid dependency. These findings are hypothesis-generating and require prospective validation with a larger sample size before clinical application.

Achieving disease clearance, which includes symptomatic, endoscopic, and histological remission, is a key step toward comprehensive disease control in the treatment of ulcerative colitis (UC). Early achievement of disease clearance by Week (W)12 of mirikizumab (miri) treatment has been associated with improved W52 clinical outcomes. This study investigates the effect of up to 4 years of miri treatment on disease clearance achievement and its sustained achievement over time in the W52 miri maintenance remitters who entered LUCENT-3 (NCT03519945), an open-label extension study. Among 868 participants who received miri induction therapy in the LUCENT clinical trial program, 544 achieved clinical response at W12. Of these, 365 were rerandomized to blinded miri maintenance, and 179 achieved clinical remission at W52 and entered the open-label extension (W52 maintenance remitters). The disease clearance response rates of W52 maintenance remitters at W52 (1 year), W104 (2 years), W152 (3 years), and W212 (4 years) were analyzed. Pre-specified disease clearance (DC) was defined as symptomatic remission [Mayo stool frequency (SF)=0, or SF = 1 with a ≥ 1 point decrease from baseline, and rectal bleeding (RB)=0], and histologic-endoscopic mucosal remission [HEMR: histologic remission (Geboes score ≤2B.0) and endoscopic remission (Mayo endoscopy subscore (ES) of 0 or 1, excluding friability)]. Disease clearance was further evaluated using a more stringent definition (sDC): symptomatic remission, histologic remission, and endoscopic normalization (ES of 0). Outcomes were analyzed using modified non-responder imputation (mNRI) and observed cases (OC) to handle missing data. Among the W52 maintenance remitters, the proportions of patients achieving DC with continuous miri treatment at years 1, 2, 3, and 4 were 75.6%(mNRI)/75.4%(OC), 65.5%/71.1%, 63.1%/72.5%, and 50.2%/62.9%, respectively (Figure 1). The proportions of W52 maintenance remitters achieving sDC with continuous miri treatment at years 1, 2, 3, and 4 were 34.5%/33.7%, 36.9%/39.4%, 38.9%/46.6%, and 30.3%/42.3%, respectively (Figure 2). Miri is the first anti-interleukin-23 p19 antibody to demonstrate consistent and sustained disease clearance in patients with moderately to severely active ulcerative colitis over four years of treatment. At year 4, more than 60% of W52 maintenance remitters achieved DC, and over 40% achieved the more stringent sDC (OC). Achieving sDC is an important milestone, as it is associated with a reduced risk of disease progression and is a key component of comprehensive disease control in UC. These results support the long-term efficacy and clinical relevance of miri in the management of ulcerative colitis. Conflict of interest Magro, Fernando: Fernando Magro served as speaker and received honoraria from Abbvie, Arena, Biogen, Bristol-Myers Squibb, Falk, Ferring, Hospira, Janssen, Laboratórios Vitoria, Pfizer, Lilly, Merck Sharp & Dohme, Sandoz, Takeda, UCB, Vifor. Danese, Silvio: Personal Fees: AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, Vifor Lecture fees from Abbvie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer, Takeda Siegmund, Britta: Grant: Pfizer Other: Consultant: Abbvie, Abivax, Boehringer Ingelheim, Bristol Myers Squibb, Dr. Falk Pharma, Eli Lilly, Endpoint Health, Galapagos, Janssen/Johnson & Johnson, Materia Prima, MSD, Pfizer, Takeda, Wedbush Securities. Speaker: Abbvie, AlfaSigma, Bristol Myers Squibb, CED Service GmbH, Dr. Falk Pharma, Eli Lilly, Ferring, Galapagos, Janssen/Johnson & ampJohnson, MD Education, MSD, Pfizer, Tr1xBio. Kobayashi, Taku: Grant: AbbVie, Alfresa Pharma, Bristol Myers Squibb, Celtrion, EA Pharma, Gilead Sciences, Kyorin Pharmaceutical, Miyarisan, Mochida Pharmaceutical, Nippon Kayaku, Otsuka Holdings, Pfizer, Sekisui Medical, Takeda, Zeria Pharmaceutical Personal Fees: AbbVie, Alfresa Pharma, Alimentiv, Bristol Myers Squibb, Celltrion, Covidien, EA Pharma, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Gilead Sciences, Janssen, JIMRO, Kissei Pharmaceutical, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, MSD, Nippon Kayaku, Pfizer, Sekisui Medical, Takeda Pharmaceutical, Zeria Pharmaceutical Siegel, Corey: Consultant/Advisory Board: Abbvie, Boomerang, Celltrion, Johnson and Johnson, Lilly, Napo Pharmaceuticals, Path Healthcare, Pfizer, Prometheus Labs, Sanofi, Takeda, Trellus Health Speaker for CME activities: Abbvie, Johnson & Johnson, Pfizer, Takeda Grant support: Abbvie, Celltrion, Johnson & Johnson, Lilly, Pfizer Intellectual property: MiTest Health, LLC (software company) has a patent for a “System and Method of Communicating Predicted Medical Outcomes.” Equity Interest: Dr. Corey Siegel and Dr. Lori Siegel are co-founders of MiTest Health, LLC (software company). Technology developed by MiTest Health, LLC has been licensed to Takeda. Dr. Corey Siegel has an equity interest in Path Healthcare. Dr. Corey Siegel has an equity interest in Trellus Health Jairath, Vipul: Consulting Fees: Abbvie, Alimentiv, Amgen, Anaptys Bio, Asahi Kasei, Asieris, Astra Zeneca, Attovia, Blackbird Labs, BMS, Boehringer Ingleheim, Biomebank, Caldera, Calluna, Catalytic Health, Celltrion, Ensho, Enthera, Exeliome Biosciences, Ferring, Fresenius Kabi, Gilead, Granite Bio, GSK, Janssen, Lilly, Merck, Mountainfield, MRM Health, Nxera, Organon, OSE Immunotherapeutics, Pendopharm, Pioneering Medicine, Pfizer, Prometheus, Roche/Genentech, Sanofi, SCOPE, Shattuck Labs, Sorriso, Spyre, Synedgen, Takeda, Teva, Tillotts, Union Therapeutics, Ventus, Ventyx, Vividion, Xencor, Zealand Pharma. Pellanda, Paola: employees and shareholder of Eli Lilly and Company Keohane, Anthony: employee of HaaPACS GmbH Duan, Yajie: Employee and shareholder of Eli Lilly and Company Arora, Ravneet: Employee and shareholder of Eli Lilly and Company. Redondo, Isabel Maria: employee and share holder Eli Lilly Colombel, Jean-Frédéric: Grant: AbbVie, Janssen Pharmaceuticals, Takeda, Prometheus and Bristol Myers Squibb Lectures from: AbbVie, Roche and Takeda Other: AbbVie, Amgen, AnaptysBio, Allergan, Apini, Arena Pharmaceuticals, Astellas, Boehringer Ingelheim, Bristol Myers Squibb, candidrx Celgene, Celltrion, Clearview Curogen, Eli Lilly, Envision Pharma Ferring Pharmaceuticals, Galmed Research, Glaxo Smith Kline, Roche, Janssen Pharmaceuticals, Kaleido Biosciences, Immunic, Iterative Scopes, Landos, Microba Life Science, Merck, Mirador, Novartis, Otsuka Pharmaceutical, Owkin, Pfizer, Protagonist Therapeutics, Sanofi, Sun Pharma, Takeda, Teva, TiGenix, and is holding stock options in Intestinal Biotech Development

The management of localized ileocecal Crohn’s disease (CD) requires balancing escalation of medical therapy against early surgical resection. While clinical phenotyping guides initial management, standard assessments often fail to distinguish reversible inflammation from irreversible fibrosis. This limitation remains a major barrier to personalized care. This narrative review aims to review current evidence on clinical features, imaging modalities, and biomarkers relevant to intestinal fibrosis and to propose a phenotype-driven framework for treatment selection in localized ileocecal CD. To address this, we synthesized current literature on intestinal fibrogenesis, cross-sectional imaging (magnetization transfer MRI (MT-MRI), shear wave elastography (SWE)), and therapeutic outcomes. Evidence was integrated to develop a conceptual algorithm incorporating disease phenotype, quantitative imaging markers, and multidisciplinary decision-making. The proposed two-tiered framework begins with the Montreal classification (Tier 1). B1 phenotypes are directed toward early intensive treat-to-target medical strategies, while B3 phenotypes may require individualized surgical management, sometimes preceded by short-term medical optimization depending on complication severity. For the challenging B2 phenotype, we propose a precision medicine pathway (Tier 2) utilizing quantitative imaging, such as MT-MRI or SWE. This pathway is intended to help stratify B2 strictures into fibrosis-dominant, inflammation-dominant, or indeterminate phenotypes within a multidisciplinary decision-making process. A phenotype-driven approach incorporating clinical and imaging information may help inform therapeutic decision-making across the spectrum of ileocecal CD, particularly in the management of stricturing disease. The proposed framework provides a roadmap for prospective validation and future clinical trials aimed at optimizing treatment selection in stricturing disease.

BACKGROUND:Older adults with ulcerative colitis (UC) have unique treatment challenges. Ozanimod is approved for the treatment of moderately to severely active UC in adults based on the phase 3 True North (TN) study results. Here, we analyzed the impact of patient age on ozanimod safety and efficacy in TN and during the open-label extension (OLE). METHODS:Patients were stratified by age at TN baseline: <40, 40 to 60, and >60 years (cutoff: 75 years). Safety was evaluated in all patients during TN and the OLE; efficacy was assessed at weeks 10 and 52 in TN and up to OLE week 190 in patients who entered as TN week 52 ozanimod clinical responders. RESULTS:Of 1012 patients analyzed, 492 were <40 years of age, 404 were 40 to 60 years of age, and 116 were >60 years of age. Infection, malignancy, cardiac events, and macular edema were low throughout TN across all ages. Exposure-adjusted incidence rates (EAIRs) of opportunistic and serious infections increased with age during the OLE. Patients ≥40 years of age had higher hypertension EAIRs than those <40 years of age, but EAIRs of other cardiovascular TEAEs were low. No cases of progressive multifocal leukoencephalopathy occurred over 242 weeks of ozanimod exposure. Efficacy rates for evaluated clinical and mucosal endpoints at weeks 10 and 52 with ozanimod were generally consistent across age groups with the overall population; similar trends were observed in the OLE. CONCLUSIONS:Ozanimod safety was similar and efficacy was generally comparable across age groups, although statistical significance vs placebo was not achieved in patients >60 years of age.

Background:Clinical symptoms do not necessarily align with disease activity in ulcerative colitis (UC). It remains unclear whether patient-reported outcomes (PROs), particularly quality of life (QOL) measures, can help characterize clinically meaningful subphenotypes among Japanese patients with UC in remission. This study aimed to identify and characterize UC subphenotypes using clustering analysis. Methods:We used data from a multicenter, prospective UC patient registry in Japan, called "YOu and Ulcerative colitis: Registry and Social network (YOURS)" (December 2018-June 2022). We assessed laboratory values and PRO data, including clinical symptoms and QOL data (e.g., fatigue, anxiety, disease-specific QOL), of patients with UC in remission. Discovery (N = 365) and replication (N = 982) datasets were independently created and subjected to clustering analysis. Data were standardized for sex (a potential confounder for various measures). Findings:PRO data correlated poorly with traditional clinical laboratory parameters. Three reproducible clusters were detected in both datasets: one cluster was characterized by lower QOL and average laboratory profiles, while the other two clusters showed preserved QOL scores either with or without distinct laboratory profiles. The cluster with lower QOL and average laboratory profiles demonstrated increased relapse rates during a 3-year follow-up in each dataset compared with the respective other two clusters. Interpretation:PRO assessments offer unique, clinically relevant data, distinct from routine biomarkers and clinical scores. Stratifying patients with UC using combined QOL and clinical laboratory parameters may help identify patients at higher risk of relapse and warrants further evaluation for its potential role in clinical decision-making. Funding:This study was funded by Takeda Pharmaceutical Company Limited.

INTRODUCTION:Anti-integrin αvβ6 (anti-αvβ6) autoantibodies serve as a diagnostic biomarker and are associated with poor prognosis in ulcerative colitis (UC). We aimed to investigate whether anti-αvβ6 autoantibody levels predict treatment outcomes of advanced therapies in patients with moderately to severely active UC. METHODS:Anti-αvβ6 autoantibody levels were measured using prospectively collected serum samples at the initiation of advanced therapies. The primary outcome was treatment persistence up to 1 year; secondary outcomes included clinical remission rates at weeks 2, 6, 14, 24, and 48, comparing low-level and high-level groups stratified by an optimal cutoff from receiver operating characteristic analysis. RESULTS:A total of 144 patients were analyzed (121 [84.0%] with extensive colitis and 87 [60.4%] with prior exposure to advanced therapies). The median observation period was 10 months, and treatment discontinuation occurred in 70 patients (48.6%). Treatment persistence was significantly higher in the low-level group (log-rank test, P = 0.002), and multivariable Cox analysis identified low antibody levels as the only independent predictor (hazard ratio, 1.90; 95% CI, 1.09-3.32). Clinical remission rates were consistently higher in the low-level group throughout all time points, with the greatest difference at week 6 (47.5% vs 20.0%; χ 2 test, P = 0.003). Low antibody levels remained an independent predictor of remission at all time points. DISCUSSION:Anti-αvβ6 autoantibodies predicted both treatment persistence and clinical remission after advanced therapies, highlighting their potential as a predictive biomarker in patients with active UC.

BACKGROUND & AIMS:Prolonged washout periods between advanced therapies and investigational drugs are commonly required in inflammatory bowel disease (IBD) randomized controlled trials (RCTs). These requirements restrict patient enrollment and diverge from real-world clinical practice. This study aimed to establish an international expert consensus on washout durations for advanced therapies and conventional immunosuppressants (IS) in IBD clinical trials and to propose methodological recommendations for future study designs. METHODS:An international panel of 12 IBD clinical trial experts participated in a Delphi consensus process. Agreement of ≥75% among participants was predefined as consensus. RESULTS:A total of 12 statements were approved. Consensus was reached to eliminate washout periods for conventional IS (thiopurines, tacrolimus, methotrexate, and mycophenolate mofetil). For golimumab and ozanimod, experts agreed on a 2-week washout period. For other biologics (infliximab, adalimumab, vedolizumab, ustekinumab, and anti-IL-23 agents), most participants favored a 2-4-week washout duration and for JAK inhibitors and etrasimod, participants supported a short 2-week washout, though without reaching formal consensus. Experts recommended incorporating washout-based stratification (<4 vs ≥4 weeks) at randomization into future trial designs to evaluate its impact on safety, pharmacokinetics, and efficacy outcomes. CONCLUSIONS:This international Delphi consensus highlights the need to adapt current washout practices in IBD RCTs to real-world practice. Experts supported shorter and standardized washout durations-preferably less than 4 weeks-to better align with clinical practice, while maintaining patient safety. Acceptance of these recommendations by regulators could harmonize washout duration criteria, enhance recruitment efficiency, and accelerate patient access to innovative therapies without compromising safety.

BACKGROUND:This study aimed to develop predictive models for acute severe ulcerative colitis (ASUC) using data from East Asian (EA) patients and to validate their performance in an Australia/New Zealand (ANZ) cohort. METHODS:A retrospective international study was conducted across 23 referral hospitals in EA and ANZ, enrolling consecutive ASUC patients between January 2015 and December 2022. Logistic regression analyses were used to construct predictive models for 1-year colectomy and non-response to corticosteroid therapy (NRS). RESULTS:Overall, 826 patients with ASUC were included (411 EA and 415 ANZ). Among EA patients, independent predictors of 1-year colectomy included female sex, prior exposure to tumor necrosis factor inhibitors, and admission albumin ≤3 g/dL. Independent predictors of NRS in the EA cohort were age at diagnosis  ≤37 years, baseline steroid use, admission albumin ≤2.5 g/dL, and the presence of extraintestinal manifestations. The EA-derived scoring systems demonstrated strong predictive performance within the EA cohort (1-year colectomy: P < .0001; NRS: P = .001) but showed limited utility in the ANZ cohort (P = .106 and P = .012). In contrast, European-developed models-including the French 1-year colectomy score and the ADMIT-ASC index for NRS-accurately predicted outcomes in the ANZ cohort (P = .007 and P < .0001) but had reduced predictive capacity in the EA cohort (P = .106 and P = .026). These findings were consistent in both cohorts following propensity score matching. CONCLUSIONS:Predictive factors for ASUC differ substantially between EA and ANZ patients, highlighting the need for population-specific predictive tools.

Background/Aims:There is limited evidence for ozanimod, an oral sphingosine 1-phosphate receptor modulator, in patients with ulcerative colitis (UC) before treatment is escalated to an immunomodulator (IM) or advanced therapy (AT), including biologics and Janus kinase inhibitors. Methods:We performed post hoc analyses to examine the efficacy and safety of ozanimod 0.92 mg versus placebo in a subgroup of Japanese IM-/AT-naive patients with moderately to severely active UC, without concomitant corticosteroids (CS), enrolled in the randomized J-True North study. Results:The analyses comprised 29 and 30 patients treated with ozanimod 0.92 mg and placebo, respectively. The clinical response rate was significantly greater in the ozanimod group at Week 12 (75.9% vs. 40.0%; P=0.0103) and Week 52 (62.1% vs. 16.7%; P=0.0010). Clinical remission, endoscopic improvement, and histologic remission rates at Weeks 12 and 52 were significantly better in the ozanimod group. Changes in the rectal bleeding subscore, stool frequency subscore, symptomatic response, and symptomatic remission were apparent by Week 2 in both groups, and tended to be better in the ozanimod group from Week 5 onward. Treatment-emergent adverse events occurred in 79.3% and 63.3% of patients in the ozanimod and placebo groups, respectively; the most frequent were nasopharyngitis (ozanimod vs. placebo: 17.2% vs. 13.3%) and pyrexia (13.8% vs. 10.0%, respectively). Conclusions:This subgroup analysis demonstrated that ozanimod 0.92 mg was significantly more effective than placebo in Japanese IM-/AT-naive UC patients without concomitant CS therapy, consistent with the results of global trials. The safety profile of ozanimod 0.92 mg was consistent with prior studies. ClinicalTrials.gov (NCT03915769) and the Japan Registry of Clinical Trials (jRCT2080224654).

Background: Clinical symptoms do not necessarily align with disease activity in ulcerative colitis (UC). It remains unclear whether patient-reported outcomes (PROs), particularly quality of life (QOL) measures, can help characterize clinically meaningful subphenotypes among Japanese patients with UC in remission. This study aimed to identify and characterize UC subphenotypes using clustering analysis. Methods: We used data from a multicenter, prospective UC patient registry in Japan, called “YOu and Ulcerative colitis: Registry and Social network (YOURS)” (December 2018-June 2022). We assessed laboratory values and PRO data, including clinical symptoms and QOL data (e.g., fatigue, anxiety, disease-specific QOL), of patients with UC in remission. Discovery (N=365) and replication (N=982) datasets were independently created and subjected to clustering analysis. Data were standardized for sex (a potential confounder for various measures). Findings: PRO data correlated poorly with traditional clinical laboratory parameters. Three reproducible clusters were detected in both datasets: one cluster was characterized by lower QOL and average laboratory profiles, while the other two clusters showed preserved QOL scores either with or without distinct laboratory profiles. The cluster with lower QOL and average laboratory profiles demonstrated increased relapse rates during a 3-year follow-up in each dataset compared with the respective other two clusters. Interpretation: PRO assessments offer unique, clinically relevant data, distinct from routine biomarkers and clinical scores. Stratifying patients with UC using combined QOL and clinical laboratory parameters may help identify patients at higher risk of relapse and warrants further evaluation for its potential role in clinical decision-making.

Intestinal ultrasound (IUS) enables frequent, noninvasive assessment of inflammatory activity in ulcerative colitis and can support treat-to-target decisions without bowel preparation. Evidence from prospective cohorts indicates that early IUS changes within 1 to 2 weeks-particularly reductions in bowel wall thickness and color Doppler vascularity-are associated with shortterm response and can guide timely treatment optimization during induction. Follow-up assessments at 6 to 12 weeks further improve risk stratification by reassessing bowel wall thickness and Doppler vascularity, including composite indices such as the Milan Ultrasound Criteria, which correlate with endoscopic outcomes and subsequent medium- to long-term clinical events (e.g., relapse and colectomy). This review synthesizes the most reproducible IUS parameters and proposes a practical, time-windowed monitoring approach integrating IUS with symptoms, biomarkers, and endoscopy, whereby assessments within 1-2 weeks and again at 6-12 weeks provide actionable information to accelerate induction optimization and anticipate later outcomes in ulcerative colitis.