ABSTRACTAimsTo determine whether the performance of leucine‐rich α2‐glycoprotein (LRG) as a biomarker for disease activity in patients with ulcerative colitis (UC) may depend on the extent of the disease.Methods and ResultsWe evaluated the correlation between various biomarkers, including the serum biomarker LRG, and endoscopic activity in 171 patients with UC. Patients were categorized into two groups based on disease extent: patients with pancolitis and those with left‐sided colitis and proctitis. LRG demonstrated similar diagnostic accuracy compared to fecal markers in patients with UC exhibiting pancolitis (area under the curve [AUC] for predicting endoscopic mucosal healing: LRG, 0.92; fecal immunochemical testing [FIT], 0.95; and fecal calprotectin [Fcal], 0.96) (FIT vs. LRG, p = 0.886; Fcal vs. LRG, p = 0.412). Conversely, for patients with left‐sided colitis and proctitis, fecal markers outperformed LRG in predicting endoscopic mucosal healing (AUC: LRG, 0.66; FIT, 0.94; and Fcal, 0.92) (FIT vs. LRG, p < 0.001; Fcal vs. LRG, p = 0.004).ConclusionOur results support selecting biomarkers according to disease extent for the management of inflammatory bowel disease. In patients with UC and pancolitis, LRG is a viable alternative when fecal samples are not feasible. Conversely, for patients with left‐sided colitis and proctitis, fecal markers with high diagnostic accuracy are recommended.

Abstract Background Interleukin-23 (IL-23)p19 inhibitors are an important modality for management of moderate-severe inflammatory bowel disease (IBD), yet intra-class comparative data remains limited with no direct head-to-head trials comparing IL-23p19 inhibitors within class. We conducted a network meta-analysis (NMA) comparing the efficacy and safety of guselkumab, mirikizumab, and risankizumab in Crohn’s disease (CD) and ulcerative colitis (UC). Aims To compare induction and maintenance outcomes in IBD across IL-23p19 inhibitors. Methods Following PRISMA-NMA guidelines, 5 databases were searched to July 2025 for randomized control trials. Outcomes included clinical response/remission, endoscopic response/remission, and adverse events (AEs). Random-effects NMAs were used to estimate relative risks (RRs) with 95% confidence intervals (CIs). Non-randomized studies were excluded. Results Fifteen trials (n = 11,166) formed connected networks including IL-23p19 agents, placebo, and ustekinumab. Across IBD subtypes, all IL-23p19 inhibitors were superior to placebo for clinical and endoscopic outcomes. In CD, guselkumab ranked highest in clinical response among biologic-exposed patients (RR 2.89, 95% CI 1.60-5.21) and achieved the largest effect in endoscopic remission (RR 6.57, 4.04-10.70). However, among biologic-naïve patients, ustekinumab led in clinical response (RR 2.37, 1.44-3.90). In UC, guselkumab showed the greatest efficacy for clinical remission (RR 2.67, 1.92-3.73), and mirikizumab ranked highest for endoscopic response (RR 3.47, 1.45-8.28). Overall AE rates were similar across agents, though serious AEs were lower with mirikizumab (RR 0.56, 0.40-0.77) and guselkumab (RR 0.62, 0.46-0.84). Conclusions IL-23p19 inhibitors are effective for both induction and maintenance therapy in IBD. Within this class of biologics, Guselkumab demonstrates the most consistent and robust efficacy across outcomes, while mirikizumab offers a favourable safety profile and the strongest endoscopic healing in UC. Relative risks (RR) for clinical response to IL-23p19 inhibitors compared to placebo in Crohn’s disease. In head-to-head comparisons, guselkumab was significantly more effective than mirikizumab (1.60 [1.11-2.29]) and risankizumab (1.67 [1.14-2.45]), but comparable to ustekinumab (0.97 [0.73-1.29]). Funding Agencies None

Proton pump inhibitors (PPIs) are standard therapy for gastroesophageal reflux disease (GERD), but long-term use causes dysbiosis, gastrointestinal side effects, and symptom relapse after discontinuation. Probiotics may offer adjunctive benefits by modulating the gut ecosystem. The study aimed to evaluate the efficacy of a multi-strain probiotic (Lihuo) with rabeprazole in GERD and its impact on gut microbiota and metabolome. A randomized, double-blind, placebo-controlled trial was conducted in 120 GERD patients assigned to receive rabeprazole with either Lihuo (n = 64) or placebo (n = 56) for 8 weeks, followed by 4 weeks of probiotic or placebo alone. The primary outcome was change in the Reflux Disease Questionnaire (RDQ) score. Secondary outcomes included Gastrointestinal Symptom Rating Scale, endoscopic healing, and multi-omics profiling (shotgun metagenomics, phageome, and untargeted/targeted metabolomics). Compared with the placebo group, the probiotic group exhibited a pronounced 36.51% reduction in RDQ scores after 12 weeks of intervention (P = 0.017), alongside a higher numerical endoscopic healing rate (36.84% vs 12.50%; P = 0.365). Metagenomics revealed enrichment of Bifidobacterium animalis, Lactiplantibacillus plantarum, and Clostridium sp900540255, with reductions in Bacteroides uniformis and Clostridium Q fessum. Metabolomics showed increased γ-aminobutyric acid, succinate, citrulline, and short-chain fatty acids levels, with interesting microbe-metabolite correlations such as Bifidobacterium animalis-γ-aminobutyric acid and Bacteroides fragilis-succinate (r ≥ 0.30, P < 0.01). Our findings support that adjunctive probiotic therapy sustains post-PPI symptom relief, associated with targeted modulation of gut microbiota and bioactive metabolites.IMPORTANCELong-term proton pump inhibitor use in gastroesophageal reflux disease (GERD) may disrupt gut microbiota and cause symptom relapse after discontinuation. We found that adjunctive probiotic therapy sustained reflux reduction post-proton pump inhibitor. Probiotic use enriched beneficial taxa (Bifidobacterium and Lactiplantibacillus plantarum) and increased γ-aminobutyric acid, succinate, citrulline, and short-chain fatty acids. Strong correlations linked microbial shifts to metabolic and clinical improvements. This study demonstrates that adjunctive probiotic therapy enhances symptom control and supports microbial-metabolic homeostasis in GERD.CLINICAL TRIALSThis study is registered with the Chinese Clinial Trial Registry as ChiCTR2000038409.

Abstract INTRODUCTION Mucosal healing in ulcerative colitis (UC) is a validated therapeutic goal linked to sustained clinical remission and decreased colectomy rates. Both biologics and small molecule inhibitors (SMIs) are approved for moderate-to-severe UC; however, comparative data regarding their effectiveness in achieving endoscopic healing remain limited and fragmented. Aim This study aimed to compare the mucosal healing efficacy of biologic therapies and SMIs in UC through a pooled analysis of randomized controlled trials (RCTs), with emphasis on endoscopic endpoints and safety profiles. METHODS A systematic review and meta-analysis was performed per PRISMA guidelines. Databases searched included PubMed (2020–2025), Cochrane Central (2010–2025), and Google Scholar (2015–2025). RCTs evaluating biologics (n = 4) or SMIs (n = 3) versus placebo or standard care in adult UC patients were included. The primary outcome was mucosal healing, defined as a Mayo endoscopic subscore ≤1. Secondary outcomes included treatment-related adverse events (AEs). Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using random-effects models. Statistical heterogeneity was assessed with the I2 statistic. RESULTS Seven RCTs comprising 2,103 patients were included. • Biologics significantly improved mucosal healing compared to control (RR: 1.68; 95% CI: 1.24–2.27; I2 = 46%). • SMIs also showed a significant effect (RR: 1.55; 95% CI: 1.19–2.03; I2 = 35%). • Indirect comparison between biologics and SMIs revealed no significant difference (RR: 1.08; 95% CI: 0.83–1.41). • Adverse events were comparable between groups (pooled RR: 1.03; 95% CI: 0.89–1.19; I2 = 21%). • Subgroup analysis indicated a more rapid onset of response with SMIs, particularly tofacitinib. CONCLUSION Biologics and SMIs both confer significant benefits in promoting mucosal healing in UC. No therapeutic class demonstrated clear superiority in efficacy or safety. Clinical decision-making should integrate patient-specific factors such as response kinetics, adverse event risk, and prior treatment exposure. These findings underscore the necessity for direct comparative trials to further refine treatment algorithms in ulcerative colitis.

STRIDE (selecting therapeutic targets in inflammatory bowel disease) established evidence-based targets for treat-to-target strategies in IBD. STRIDE-II designates clinical remission, C-reactive protein (CRP) normalization, and fecal calprotectin (FC) reduction as short- to intermediate-term targets, and mucosal healing as a long-term target. This study evaluated STRIDE-II application and disease control in a real-world pediatric cohort. We retrospectively analyzed newly diagnosed pediatric IBD patients (ages 3-18 years) treated according to guidelines between June 2017 and January 2023. Time-to-reach STRIDE-II targets and time-to-first flare were assessed over 52 weeks using disease activity indices, inflammatory biomarkers (CRP, FC), and endoscopy. Seventy-four patients were included (37 Crohn's disease [CD], 37 ulcerative colitis [UC]). All CD patients received primary maintenance therapy with immunomodulators or biologics, versus 51% UC patients. Clinical remission and CRP normalization occurred within 5-10 weeks; FC normalization within 12-19 weeks. By 6 months, combined targets (clinical remission plus CRP and FC normalization) were achieved by 54% of CD patients and 43% of UC patients. Clinical relapse after remission occurred more frequently in UC than in CD (67% vs. 43%, p = 0.0334). Follow-up endoscopy at a median of 41 weeks (CD) and 52 weeks (UC) showed endoscopic healing in 7/18 (39%) CD and 13/22 (59%) UC patients. Most pediatric IBD patients achieved clinical remission and CRP normalization within STRIDE-II timeframes, whereas FC normalization occurred later, and relapses-particularly in UC-remained common. The notable proportion of patients with suboptimal disease control underscores the need for continuous monitoring in pediatric IBD.

Abstract Background Crohn’s disease (CD) is characterized by transmural inflammation and achieving transmural healing (TH) indicated by absence of inflammation on imaging study or endoscopy may lead to improved long-term outcomes. However, evidence supporting this hypothesis is limited. Methods Adult patients diagnosed with CD who underwent ileocolonoscopy and cross-sectional imaging within 6 months were included. Long-term outcomes of CD-related surgery and hospitalization in patients with TH (definition of both endoscopic healing and radiological healing), endoscopic healing (EH: absence of ulceration on ileocolonoscopy) alone, radiological healing (RH: no sign of active inflammation on imaging study) alone, and no healing (NH: presence of inflammation on both ileocolonoscopy and cross-sectional imaging) were assessed. We used Cox proportional hazards models and modified Poisson regression Results Among 180 included patients 40.5% were males and the mean disease duration was 12.5 years. Of these patients, 26.7% achieved TH, 21.1% EH, 12.8% RH and 39.4% classified as NH. At baseline, 54.4% were on biologics which increased to 81.7% at last follow-up (76-78 months across groups). Cumulative probabilities of surgery were lowest in patients with TH (0%, 2.3%, 7.0% at 1, 3, and 5yrs) and highest in patients with NH (13%, 20.5%, 26.9%). On Cox proportional hazard regression analysis, TH was associated with a significantly reduced risk of CD-related surgery (HR 0.01, 95%CI [0.00–0.35], p = 0.009) compared to NH. The probabilities of surgery were numerically lower for patients with RH compared to EH (10% vs. 13.2%, 10% vs. 18.4% and 21.2% vs. 26.9% at 1, 3 and 5yrs). Probabilities of CD related hospitalization were lowest with TH (4.3%, 8.8% and 13.6% at 1, 3 and 5yrs) Conclusion Transmural healing was associated with superior long-term outcomes compared to endoscopic or radiologic healing alone. Future studies should focus on standardizing its definition and evaluate treat-to-target strategies Conflict of interest: Dr. Vuyyuru, Sudheer: Received consulting fee from Alimentiv Inc Goodwin, Shane: None Solitano, Virginia: Speaker’s fees from Pfizer, Takeda, Giuliani, Tillotts Pharma consulting fees from J &amp; J travel grant from Abbvie Ramsewak, Daryl: None Kassam, Zahra: has received consulting fees from Alimentiv Inc and Bayer Inc. Townsend, Cassandra: has received advisory board fees from Celltrion, Pendopharm and Takeda Gregor, James: received speakers fees from AbbVie, Janssen, Takeda, Celltrion, Organon and Ferring Beaton, Melanie: Melanie Beaton has received advisory board or consultancy from AbbVie, Celltrion, Ferring, Janssen, Novo Nordisk, Pfizer, and Takeda. She has participated in clinical trials with AbbVie, Novo Nordisk, Gilead, Takeda, Janssen, Pfizer and Astra Zeneca Crowley, Eileen: Grant: Research grant from Abbvie &amp; Pfizer Personal Fees: Consulting fees from Alimentiv Inc. &amp; Sanofi (Advisory board) Alkhattabi, Maan: None Sey, Michael: has received consultant fees from Medtronic research grants and speaker fees from Pendopharm educational grant from Cook Medical. 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.

Abstract Background The armamentarium of therapy in IBD continues to expand along with the characteristics of these therapies. Concurrently, treatment targets also continue to broaden. The study aim was to measure child and parent preferences on treatment characteristics and treatment goals in management of pediatric IBD. Methods Based on prior qualitative work (deBruyn et al. 2025; currently under review), we developed an online survey to elicit treatment preferences for IBD management among children and their parents. Children with established IBD (ages 11 to 18 years) and parents were recruited at 7 centers across Canada. The survey included a discrete-choice experiment (DCE) presenting two unlabelled treatment options that varied by (a) mode of administration (pill, infusion, injection, rectal enema or suppository), (b) chance of clinical remission at 1 year (20%, 60%, 80%), and (c) chance of endoscopic remission at 1 year (20%, 30%, 60%). A best-worst scaling (BWS) exercise was included to rank 7 treatment goals (symptom improvement, normal blood biomarkers, normal stool biomarkers, endoscopic healing, histologic healing, transmural healing, return to normal life). Preliminary data of the pilot testing were collected and analyzed separately for children and parents using multinomial logit models (for the DCE) and count analyses (for the BWS) with planned analysis of the full sample (124 children and 268 parents) to come. Results A total of 82 respondents were included in the preliminary analyses (51 children [62% Crohn’s disease, 62% female]; 31 parents [90% without personal history of IBD]). Overall, children and parents showed similar treatment preferences in the DCE as well as BWS treatment goal rankings. Children and parents preferred 80% chances of clinical remission and 60% chances of endoscopic remission over 20% chances of clinical and endoscopic remission. Children preferred oral treatments while parents preferred infusions and injections over rectal treatments. Return to normal life and symptom improvement were ranked as the most important treatment goals, while the least important treatment goal was histologic healing. Endoscopic, transmural and histologic healing were the least important aspects for parents whereas only endoscopic and histologic healing were ranked as least important treatment goals for children. Conclusion Our preliminary analysis of pilot data reveals that preferences for treatment characteristics and goals were similar between children and parents. However children valued an oral treatment and transmural healing more highly than parents. Our planned full analysis yields the potential to enhance shared decision-making and guide development of knowledge translation tools to improve outcomes. Reference: deBruyn, J. C., Hart, L., MacKean, G., Staples, N., Lee, A., MacDonald, K. V., &amp; Marshall, D. A. (2025). Child and parent perspectives in IBD management: A literature review and qualitative study [Manuscript submitted for publication; under review]. Crohn’s &amp; Colitis 360. Conflict of interest: Dr. Debruyn, Jennifer: Personal Fees for Consulting: Abbvie, Pfizer Personal Fees for travel support for meetings: Organon Oedingen, Carina: No conflict of interest Pai, Nikhil: Received research materials from Rebyota. Otley, Anthony: Research grants - Abbvie Marshall, Deborah: Svare Chair in Health Economics, Value and Impact Non-financial support from Illumina, ISPOR for meeting travel expenses. Personal fees for DCE consultation from Novartis, Analytica and Office for Health Economics.

Abstract Background Ulcerative colitis (UC) management aims to achieve sustained clinical remission and long-term endoscopic and histological healing. In the Phase 2b/3 QUASAR trial in UC, guselkumab (GUS) significantly improved clinical remission by Week (W) 44 of the maintenance (M) study, with one-third of patients (pts) achieving endoscopic remission (ER; endoscopic Mayo subscore [EMS]=0).1 Post-hoc analyses of QUASAR evaluated predictors of ER at 1 year of GUS treatment in pts with moderately-to-severely active UC. Methods In the maintenance study of QUASAR, GUS (intravenous 200mg at W0, W4, and W8) responders at W12 of the induction study were re-randomized to receive subcutaneous (SC) GUS 100mg every 8W (Q8W), GUS 200mg SC Q4W, or placebo. Data from pts re-randomized to GUS were analyzed. Predictors of ER at M-W44 were assessed via logistic regression. Univariate models were run for each variable of interest at induction and M-baseline (BL). Variables with p &amp;lt; 0.1 were entered into reduced multivariate models using stepwise backward selection (Wald method); separate models were run for induction BL and M-BL variables. Results Of 378 GUS responders re-randomized to GUS 100mg SC Q8W or GUS 200mg SC Q4W, 129 (34%) achieved M-W44 ER. Rates of M-W44 ER did not differ across GUS regimens. In univariate models, induction BL factors associated with achieving M-W44 ER included female sex, extensive UC, concomitant oral aminosalicylate use, elevated C-reactive protein levels (CRP; &amp;gt;3mg/L), and no prior advanced drug therapy (ADT) failure (Table 1; Table 2). At M-BL, lower CRP (≤3mg/L or ≥ 50% reduction from induction BL) and fecal calprotectin (FC; ≤250μg/g or ≥ 50% reduction from induction BL) levels, and endoscopic healing (EMS=0 or 1) were also individually associated with M-W44 ER. After adjusting for GUS regimen, female sex (odds ratio [OR] [95% confidence interval; CI]: 1.8 [1.2, 2.9]; nominal P = 0.007), extensive UC (1.8 [1.2, 2.9]; nominal P = 0.007), and concomitant oral aminosalicylate use (1.9 [1.1, 3.4]; nominal P = 0.022) were identified as independent induction BL predictors of M-W44 ER. Achievement of endoscopic healing (3.1 [1.9, 4.9]; nominal P &amp;lt; 0.0001) at M-BL was independently associated with M-W44 ER. Conclusion Among GUS responders in the QUASAR maintenance study, female sex, extensive UC, and concomitant oral aminosalicylate use at induction BL were independently associated with ER at 1 year of GUS treatment. Importantly, achieving endoscopic healing after induction (i.e., at M-BL) was strongly associated with higher likelihood of ER at 1 year, irrespective of GUS dosing regimen, suggesting that this factor may help inform long-term endoscopic outcomes. Reference: 1. Rubin DT, Allegretti JR, Panés J, et al. Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies. Lancet. 2025;405(10472):33-49. doi:10.1016/S0140-6736(24)01927-5. Conflict of interest: Rubin, David T.: Grant support: Takeda Pharmaceuticals Consultant: Abbvie, Abivax SA, Altrubio, Athos Therapeutics, Inc, Bristol-Myers Squibb, Celltrion, Connect BioPharma, Eli Lilly &amp; Co., Genentech (Roche) Inc., Iterative Health, Janssen Pharmaceuticals, Johnson &amp; Johnson, Merck &amp; Co., Mirador, Odyssey Therapeutics, Pfizer, Sanofi, Spyre, Takeda Pharmaceuticals, Vedanta Biosciences, and Ventyx. Fumery, Mathurin: Grant: Pfizer Personal Fees: Abbvie, Janssen, Takeda, MSD, Biogen, Amgen, Sandoz, Fresenius, Gilead, Celgene, Galapagos, Mylan, Tillots, Ferring, Pfizer, Hospira, CTMA, Boehringer, Lilly, Arena Non-financial Support: Abbvie, Janssen, Takeda, MSD, Galapagos, Ferring, Pfizer Armuzzi, Alessandro: Consulting fees from AbbVie, Abivax, Alfa Sigma, Astra Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Enthera, Ferring, Galapagos, Gilead, Giuliani, Janssen, Lionhealth, MSD, Nestlé, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sanofi, Sandoz, Takeda, Teva Pharmaceuticals, Tillots Pharma Speaker’s fees from AbbVie, Abivax, AG Pharma, Alfa Sigma, Biogen, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, Lionhealth, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Teva Pharmaceuticals Research support from Biogen, MSD, Takeda, and Pfizer Non-financial support from Abbvie, Janssen, MSD, Pfizer, Takeda Ferrante, Marc: Research grants from AbbVie, EG Pharma, Celltrion, Janssen, Pfizer, Takeda and Viatris Consultancy fees from AbbVie, AgomAb Therapeutics, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Janssen-Cilag, MRM Health, Merck Sharp and Dohme, Pfizer, Takeda and ThermoFisher Speakers’ fees from AbbVie, Biogen, Boehringer Ingelheim, Dr Falk Pharma, Ferring, Janssen-Cilag, Merck Sharp and Dohme, Pfizer, Takeda, Truvion Healthcare and Viatris Baker, Thomas: Employee of Johnson &amp; Johnson Alvarez, Yelina: Employee of Johnson &amp; Johnson Bravatà, Ivana: Employee of Johnson &amp; Johnson Nazar, Maciek: Employee of Johnson &amp; Johnson Van Denderen, Jacqueline: Employee of Johnson &amp; Johnson Mccaffrey, Victoria: Employee of Johnson &amp; Johnson Atreya, Raja: RA has served as a speaker, or consultant, or received research grants from AbbVie, Abivax, AlfaSigma, Arena Pharmaceuticals, Astra-Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion Healthcare, Dr Falk Pharma, Galapagos, Gilead, GlaxoSmithKline, InDex Pharmaceuticals, Johnson &amp; Johnson, Lilly, Materia Prima, Merck Sharpe &amp; Dohme, Pfizer, Roche Pharma, Takeda Pharma, Viatris.

Proactive Drug Monitoring Versus Clinically Based Dosing for Endoscopic Healing in Pediatric Crohn's Disease Receiving Infliximab.

Abstract Background To assess the rates of clinical response at week 8, biochemical response, steroid-free clinical remission, endoscopic healing and safety outcomes at week 26 with upadacitinib in biologic-naïve patients with moderate to severe Ulcerative Colitis (UC). Methods This was a retrospective analysis of prospectively collected data extracted from the notes of biologic-naïve patients with moderate to severe UC who were treated with upadacitinib during the last year in five Greek IBD centres and who had a follow-up of at least 26 weeks after initiation of treatment. Upadacitinib was administered at a dose of 45 mg once daily for 8 weeks followed by a maintenance dose of 30 mg once daily thereafter. Week-8 clinical response was defined as the reduction in the partial Mayo score by at least 2 points, without concomitant use of any steroid preparation (budesonide, prednis(ol)one, or methylprednisolone). Steroid-free clinical remission at week 26 was defined as a partial Mayo score of ≤ 1 point without concomitant use of any steroid preparation. Biochemical response at week 26 was defined as any reduction in faecal calprotectin or plasma C-reactive protein concentrations compared with their baseline levels. Mucosal healing at week 26 was defined as a Mayo endoscopic subscore of ≤ 1. A safety list of all reported adverse events was recorded. Treatment discontinuation due to adverse events was considered as treatment failure, whereas patients needing escalation of the maintenance dose were also considered as non-responders. Results Overall, 36 patients (21 males), aged (mean ± SD) 31.9 (11.1) years and with a disease duration of (mean ± SD) 5.8 (4.9) years were included. UC was extensive in 21 patients and left-sided in 15. Clinical response was observed in 22 (61.1%) patients at week 8. Biochemical response and steroid-free clinical remission at week 26 were achieved in 25 (69.4%) patients, and endoscopic healing in 19 (52.8%) patients. Adverse events that did not lead to treatment discontinuation occurred in three patients (hyperlipidemia n = 1, elevated liver enzymes n = 1, acne n = 1). Conclusion In this retrospective, real-world ongoing cohort study, upadacitinib demonstrated clinical response at week 8 and steroid-free clinical remission at week 26 in more than 60% of biologic-naïve patients with moderate to severe UC, with a good safety profile. Conflict of interest: Mousourakis, Konstantinos: No conflict of interest Kanellopoulos, Panagiotis: Nothing to declare Kozompoli, Dimitra: No conflict of interest Kalogiros, Georgios: No conflict of interest Agorogianni, Alexandra: No conflict of interest Boumponaris, Alexandros: No conflict of interest Lazou, Dimitra: No conflict of interest Karatzas, Pantelis: No conflict of interest Michalopoulos, George: No conflict of interest Striki, Athanasia: No conflict of interest Gatopoulou, Anthia: No conflict of interest Dimitriadis, Dimitris: No conflict of interest Trimponias, Georgios Dimitrios: No conflict of interest Theodoropoulou, Angeliki: No conflict of interest Viazis, Nikolaos: No conflict of interest

Abstract Background Etrasimod is an oral, next-generation, selective modulator of sphingosine 1-phosphate receptors 1, 4, and 5, developed for the management of moderately to severely active ulcerative colitis (UC).1 This post hoc analysis evaluated the efficacy of Etrasimod 2 mg once- daily vs placebo in patients receiving prior 5-aminosalicylates and/or thiopurines in the phase 3 ENLIGHT UC study. Methods ENLIGHT UC (NCT04176588) was a randomized, double-blind, placebo-controlled, multicenter, phase 3 study in Asia adults with moderately to severely active UC and an inadequate response, loss of response, or intolerance to at least one UC therapy.2 Patients were randomized 2:1 to receive once-daily oral Etrasimod 2 mg or placebo for 12 weeks (induction period). Responders at 12 weeks were re-randomized 1:1 to Etrasimod 2 mg or placebo for 40 weeks (maintenance period). The primary endpoint, clinical remission, and secondary endpoints—endoscopic improvement, mucosal healing, and symptomatic remission—were assessed during both induction and maintenance periods. Results A total of 340 patients were included in the induction period (etrasimod vs placebo: 228 vs 112) and 157 during the maintenance period (77 vs 80) in ENLIGHT UC study. Nearly all patients (&amp;gt;99%) had previously received 5-aminosalicylates and/or thiopurines. Specifically, 99.7% were treated with 5-aminosalicylates and 7.4% with thiopurines. Among these, bio/JAKi-naïve patients treated exclusively with 5-aminosalicylates and/or thiopurines constituted the main analysis population of this post hoc analysis, accounting for 80.3% (273/340; etrasimod vs placebo: 82.5% [188/228] vs 75.9% [85/112]) of patients during induction period and 79.6% (125/157; etrasimod vs placebo: 80.5% [62/77] vs 78.8%[63/80]) during maintenance period. Significantly higher proportions of patients treated with etrasimod achieved clinical remission compared with placebo at induction week 12 (25.5% vs 2.4%; difference 23.9%, 95% CI 16.9–30.9; p &amp;lt; 0.0001) and maintenance week 40 (46.8% vs 14.3%; difference 32.6%, 95% CI 17.5–47.7; p &amp;lt; 0.0001; Table 1). Similar trends were observed for endoscopic improvement (37.2% vs 5.9% at week 12; 61.3% vs 17.5% at week 40), mucosal healing (26.6% vs 3.5% at week 12; 53.2% vs 9.5% at week 40), and symptomatic remission (39.9% vs 15.3% at week 12; 61.3% vs 31.7% at week 40), all with p &amp;lt; 0.0001. Conclusion Etrasimod was effective as an oral induction and maintenance treatment in moderately to severely active UC patients treated with prior 5-aminosalicylates and/or thiopurines, supporting its effectiveness when used early in the UC treatment algorithm.

Abstract Background There is little evidence regarding the predictive factors associated with mucosal healing in patients with moderate ulcerative colitis (UC) treated with steroids. The aim of this study was to analyse the association between the speed of improvement in clinical variables with calprotectin levels and endoscopic mucosal healing once a conventional course of steroids has been completed. Methods All patients in the GETECCU prospective randomised CECUM clinical trial who completed the endoscopic assessment at eight weeks were included. Clinical variables were collected at 7 days, and at 4 and 8 weeks: presence of rectal bleeding, urgency and nocturnal stools, Mayo and Walmsley sub-scores, and faecal calprotectin levels. Endoscopic mucosal healing at week 8 was defined as an endoscopic Mayo score of 0. Group differences were compared and the association between early clinical response and final mucosal healing was analysed using descriptive statistics and logistic regression models adjusted for baseline clinical variables. Results Of the 75 patients included in the CECUM study, 58 underwent endoscopy at week 8. Forty-eight per cent were women with a median age of 49 (range 19–79), 98 per cent were non-smokers, 52 per cent had extensive colitis and 32 per cent had previously received steroids. The mucosal healing rate at eight weeks was 29% (17 of 58). In the univariate analysis, disappearance of rectal bleeding at week 4, use of topical therapy and calprotectin levels &amp;lt;250 at day 7 and &amp;lt;150 at 4 weeks were associated with mucosal healing (p &amp;lt; 0.05). In the multivariate logistic regression, independent factors associated with mucosal healing were topical treatment at 7 days (OR 9.96; 95% CI 1.51–65.83; p = 0.017), faecal calprotectin levels &amp;lt;250 µg/g at 7 days (OR 5.48; 95% CI 1.28–23.45; p = 0.022) and calprotectin levels &amp;lt;150 µg/g at 4 weeks (OR 5.15; 95% CI 1.13–23.32; p = 0.034). Conclusion Early normalisation of calprotectin and the use of topical treatment during the first week are independent predictors of mucosal healing in steroid-treated UC with moderate activity. These results reinforce the value of calprotectin as a non-invasive clinical decision marker and, furthermore, support the use of combined topical treatment when initiating oral steroids. Conflict of interest: Mañosa Ciria, Miriam: Personal Fees: Abbvie, FAES Pharma, Ferring, Jannsen, MSD, Pfizer, Tillots and Lilly Llao Guardia, Jordina: I have received financial support from AbbVie, Tillots, Adacyte, Jansen, Alfasigma and Lilly for educational activities. Piñero, Gisela Soledad: GP has served as a speaker or has received education funding or advisory fees from Adacyte, AbbVie, Kern Pharma, Ferring, Alfasigma. Calafat Sard, Margalida: No conflict of interest Martin Arranz, Eduardo: Personal Fees: Olympus and Janssen Non-financial Support: Support for conference attendance, education or research from Abbvie, Pfizer, Janssen Zabana, Yamile: Personal Fees: AbbVie, Adacyte Therapeutics, Alfa-Sigma, Amgen, Boehringer Ingelheim, Dr Falk Pharma, FAES Pharma, Fresenius Kabi, Ferring, Galapagos, Janssen-J &amp; J, Kern Pharma, Lilly, MSD, Pfizer, Sanofi, Sandoz, Takeda, Tillots Pharma Non-financial Support: Shire, Otsuka, Almirall Navarro Llavat, Mercedes: No conflict of interest Teller, Marta: No conflict of interest Garcia Planella, Esther: No conflict of interest Busquets Casals, David: No conflict of interest Monfort Miquel, David: No conflict of interest Juan-Ramón , Pineda: No conflict of interest Gutiérrez Casbas, Ana: No conflict of interest Villoria Ferrer, Alberto: No conflict of interest Menchen Viso, Luis Alberto: No conflict of interest Bastida Paz, Guillermo: No conflict of interest Garcia Alonso, Francisco Javier: I have acted as a speaker for Abbvie, Lilly and Johnson and Johnson Rivero Tirado, Montserrat: No conflict of interest Chaparro, María: Grants: Pfizer, Janssen, Biogen, Abbvie, Lilly Personal Fees: Pfizer, Faes, Lilly, Abbvie, Janssen Riestra Menéndez, Sabino: No conflict of interest Merino Ochoa, Olga: No conflict of interest Rodríguez-Lago, Iago: No conflict of interest Barreiro-de Acosta, Manuel: MBA has been speaker, consultant and advisory member for or has received research funding from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, Alphasigma, Lilly, Pfizer, Sandoz, Biocon, Abivax, Fresenius, Faes Farma, Ferring, Tillots, Chiesi, Adacyte, Diasorin, Oncostellae and SunRock. Rodríguez-Fortúnez, Patricia: No conflict of interest Domènech Moral, Eugeni: Personal Fees: I have served as a speaker, or has received research or education funding or advisory fees from AbbVie, Adacyte Therapeutics, Biogen, Celltrion, Gilead, Janssen, Kern Pharma, MSD, Pfizer, Roche, Samsung, Takeda, Tillots. Other: I have served as a speaker, or has received research or education funding or advisory fees from AbbVie, Adacyte Therapeutics, Alfasigma/Galapagos Biogen, Celltrion, Ferring, Gilead, GoodGut, Imidomics, Janssen, Kern Pharma, Lilly, MSD, Pfizer, Roche, Takeda, Tillots.

Abstract Background Transmural healing (TH) is an emerging treatment target for IBD and is associated with superior outcomes compared to clinical or endoscopic healing. However, current paediatric proactive infliximab (IFX) therapeutic drug monitoring (pTDM) guidelines are based on clinical and biochemical outcomes. This study aimed to identify IFX trough concentration (cTrough) targets associated with TH assessed by intestinal ultrasound (IUS). Methods This cohort study included paediatric IBD patients, &amp;lt;18 years of age, who started IFX and underwent IUS as part of routine clinical care. Patients with isolated upper GI disease, proctitis or no IUS follow-up were excluded. The primary outcome was the IFX induction cTrough associated with TH, defined as a maximum bowel wall thickness (BWT) &amp;lt;2.5mm per paediatric consensus and compared with the adult &amp;lt;3.0mm definition (+/- colour doppler signal). IUS was conducted following the International Bowel UltraSound (IBUS) acquisition consensus by two IBUS-certified paediatric gastroenterologists. IFX cTrough and antibodies (ATIs) were measured at the 3rd and 4th infusion and at maintenance intervals following pTDM guidelines. IFX and ATIs were measured by LC-MS/MS and ECLIA, respectively (Mayo Clinic Laboratories). Area under the receiver operating characteristics (AUROC) analyses were used to evaluate IFX cTrough cutoffs associated with TH. Results The cohort included 66 children with IBD, 45 of whom met inclusion criteria (67 IFX cTrough-IUS pairs). Mean age 10 (IQR: 9-13) years of age, 53% (24) Crohn’s disease, and 58% (26) female. Patients with the paediatric TH target (BWT &amp;lt;2.5mm) had a higher median IFX induction cTroughs 39.5 μg/mL (24.5-50) compared to ≥ 2.5mm, 14 μg/mL (7.6-26.5; P=0.04). Patients with a maximum BWT &amp;lt;3.0 mm had higher IFX induction cTroughs 32 μg/mL (25-49) compared to ≥ 3.0mm, 14 μg/mL (7.6-23; P=0.03). At infusion-3, an IFX ≥22 μg/mL cutoff predicted TH (AUROC 0.74; sensitivity 0.80, specificity 0.80) for &amp;lt;2.5mm and (AUROC 0.78; sens 0.83, spec 0.89) for &amp;lt;3.0mm. At infusion-4, a cutoff of IFX ≥17 μg/mL (AUROC 0.75; sens 1.00, spec 0.71) predicted the paediatric TH target at &amp;lt; 2.5mm, while a cutoff of IFX ≥14 μg/mL (AUROC 0.82; sens 1.00, spec 0.75) predicted TH at the adult &amp;lt;3.0mm definition. Addition of colour doppler signal to BWT did not improve AUROC predictions. Moreover, maintenance IFX concentrations beyond infusion-4 did not predict TH. Conclusion This study identified IFX cTroughs that predict paediatric transmural healing by intestinal ultrasound. Maintenance concentrations did not predict healing. Future intervention studies should evaluate if prospective optimized dosing results in enhanced transmural healing outcomes. Conflict of interest: Toroslu, Ertug: NOTHING TO DECLARE Patel, Perseus: None Colman, Ruben: No conflicts

Abstract Background Tasty&amp;Healthy (T&amp;H) is a whole food diet shown to induce clinical and biological remission in Crohn’s disease (CD)(1). It eliminates processed foods, gluten, red meat, and dairy (except plain yogurt); no formula or mandatory components are needed. Here we aimed to evaluate whether T&amp;H diet maintenance treatment induces radiologic and endoscopic remission while gradually reintroducing gluten and dairy. Methods Patients, aged 4–37 years, achieving deep remission (MINI index&amp;lt;8 and wPCDAI&amp;lt;12.5/CDAI&amp;lt;150) in the previous TASTI-MM (T&amp;H vs. EEN) and TASTI-E (T&amp;H vs. regular diet) induction RCTs, were enrolled in this open-label maintenance trial and completed 24 weeks on the diet. Gluten and dairy were reintroduced monthly; &amp;gt;30% increase in fecal calprotectin prompted re-elimination of the specific ingredient. Intestinal Ultrasound with Segmental Activity Scoring (IUS-SAS) was performed at weeks 0, 8 and 24 and, in a subset who consented, video capsule-endoscopy (VCE) or ileocolonoscopy at week 24. Results Forty-three patients were enrolled: age 16±5.8 years, 33 children/adolescents; 91% not receiving any therapy besides T&amp;H. Clinical remission at 24 weeks was maintained in 37/43 (86%) participants; 53% successfully re-introduced gluten and dairy. All IUS parameters improved from baseline to weeks 8 and 24 ( including the maximal bowel score (IBUS-SAS 44.9 [IQR 2.1-64.9], 14 [0-48.5], 13.6 [0-34,6]; p = 0.0068) and in the terminal ileum (43 [IQR 0-64.8], 14 [0- 47.5], 5 [0-31], respectively; p = 0.0069). Among 29 patients with paired IUS assessments at baseline and week 24, 86% showed improvement or normalization of the ileal IBUS-SAS score, and 83% (24/29) demonstrated improvement in both the maximal and panenteric cumulative scores. Of the 23 patients who underwent VCE/ileocolonoscopy, 14 (61%) exhibited complete endoscopic healing or had only a few aphthous ulcers. Conclusion The T&amp;H diet, combined with structured, calprotectin-guided reintroduction of gluten and dairy, maintained clinical remission and improved radiological and endoscopic inflammation in patients up to 24 weeks. Reference: 1. Aharoni-Frutkoff Y, Plotkin L, Pollak D, et al. Whole Food Diet Induces Remission in Children and Young Adults With Mild to Moderate Crohn’s Disease and Is More Tolerable Than Exclusive Enteral Nutrition: A Randomized Controlled Trial. Gastroenterology 2025. Conflict of interest: Plotkin, Luba: No conflict of interest Aharoni-Frutkoff, Yonat: No conflict of interest Shavit, Zivia: No conflict of interest Ms. Focht, Gili: No conflict of interest Livovsky, Jessica: No conflict of interest Lev Zion, Raffi: No conflict of interest Ledder, Oren: No conflict of interest Cytter- Kuint, Ruth: No conflict of interest Zharkov, Elena: No conflict of interest Broide, Efrat: No conflict of interest Assa, Amit: No conflict of interest Sigall-Boneh, Rotem: No conflict of interest Weiss, Batia: No conflict of interest Slae, Mordechai: No conflict of interest Dotan, Iris: No conflict of interest Godny, Lihi: No conflict of interest Kierkuś, Jarosław: No conflict of interest Griffiths, Anne: No conflict of interest Naftali, Timna: No conflict of interest Aloi, Marina: No conflict of interest Yerushalmy-Feler, Anat: No conflict of interest Schwerd, Tobias: No conflict of interest Reifen, Ram: No conflict of interest Turner, Dan: No conflict of interest

Abstract Background Currently, the concept of deep remission in patients with ulcerative colitis (UC) includes not only achieving clinical remission, but also endoscopic healing of the colon mucosa and normalization of laboratory markers of inflammation. Aim: To evaluate the increase in adherence to drug therapy through psychological support to achieve endoscopic remission. Methods Medical support for patients with UC in the Department of IBD was provided by a medical psychologist. Of the 1,000 patients with UC who underwent a questionnaire to assess adherence to drug therapy, 874 (87.4%) patients were re-interviewed and clinical laboratory and instrumental studies were performed after 6 months after discharge from the hospital. Among the 874 patients who underwent repeated questioning, 498 (56.9%) had low adherence to drug therapy. 180 (20.6%) patients with UC with low adherence to drug therapy had psychological support, 318 (79.4%) patients from the low-adherence group did not have psychological support. Results According to a repeated survey of patients with UC in the group with psychological support, the level of adherence increased by 22.48%. 112 (62.2%) patients according to the Morisky-Green questionnaire had a high commitment to drug therapy after remedial sessions with a medical psychologist, 68 (37.8%) patients with UC maintained low adherence to drug therapy. therapy. In the group of patients without psychological support, according to repeated questionnaires, the level of adherence increased by 8.8%: out of 318 patients, only 44 (13.8%) increased their adherence to drug therapy, while 274 (86.2%) maintained low adherence to drug therapy (OR - 10.108; 95% CI - 6.527- 15.654; x2 - 122.848; p &amp;lt; 0.001). According to our data, there were also differences in endoscopic healing of the colon mucosa in the groups of patients with and without psychological support. Of the 180 patients in the group with psychological support, 85 (47.2%) patients had endoscopic mucosal healing (Meyo 0), and 99 (31.1%) patients in the group without psychological support (OR - 1.979; 95% CI 1.358 - 2.885; x2 - 12.092; p &amp;lt; 0.001). Conclusion Increased adherence to drug therapy through psychological support promotes Mucosal Healing. Conflict of interest: Gorodetskaya, Anait: No conflict of interest Prof. Knyazev, Oleg: No conflict of interest Kagramanova, Anna Valeryevna:

Abstract Background Treatment options for patients with mild-to-moderate ulcerative colitis (UC) failing 5-ASA are limited. MH002 is an optimized Live biotherapeutic product (LBP) consisting of 6 non-pathogenic, wellcharacterized commensal bacteria. Its anticipated mechanism is reversion of dysregulated host inflammatory mechanisms, interactions with gut microbiota, and induction of mucosal healing. Methods In this 2:1-randomized, double-blind, placebo-controlled first-in-disease study (EudraCT 2020-001355-33), 45 patients with mild to moderate active UC (Modified Mayo Score [MMS] =4-8 but including Mayo Endoscopic Sub-score [MES] ≥2) received treatment with 1.2x1010 eqCFU MH002 or placebo (PBO) once daily for 8 + 8 wks. The primary endpoint was the rate of treatment-emergent adverse events (TEAEs). Here, a post-hoc analysis investigating response based on the patients baseline characteristics is reported as well as observed alterations in fecal microbiome. Results MH002 treatment was safe and well tolerated, and resulted in clinically meaningful improvements in disease activity and inflammatory parameters1. Stratifying patients based on their MES score at baseline (MES 2 or 3), showed for MES=2, an improvement of clinical symptoms and endoscopic healing with clinical remission of 4/15 (27%) and 1/10 (10%) on MH002 and PBO, respectively. However, in patients with MES=3, while clinical symptoms and endoscopic healing improved, clinical remission was not observed at week8. Furthermore, the evolution of fecal calprotectin (FCP) levels in patients with MES=2 or MES=3 at baseline showed an earlier onset of decrease in the MES=2 group (week 2 for MES=2 and week 10 for MES=3). In terms of microbiome alterations, significant increase in α-diversity was observed with treatment response, which is indicative of eubiosis restoration. In parallel, reduction of different taxa described to be associated with IBD such as Enterobacterales, Campylobacterales and Mycobiome occurred with continued changes beyond week8 when exposed to MH002. While no depletion of background microbiome with vancomycin was included, making MH002 strain detection technically challenging, up to 4 product strains could still be detected in the MH002 treated patients. However, no link between specific strain detection patterns and therapeutic effects could be observed. Conclusion These data suggest that in order to reach clinical remission in patients with MES=3 and to reach more pronounced microbiome shifts, a treatment period longer than 8 wks may be needed. Also, absence of a vancomycin microbiome depletion allows to study the general microbiome recovery in patients. These data allow optimization of the next clinical study protocol. Reference: Vermeire S, Dewint P, Vansteelant M, et al. Safety and efficacy of MH002, an optimized live biotherapeutic product, for the treatment of mild to moderate ulcerative colitis: a first-in-disease, double-blind, randomized clinical trial. JCC. 2024, 18(S1). Conflict of interest: Conrath, Katja: paid consultant for MRM Health, shareholder of MRM Health Bolca, Selin: shareholder of MRM Health de Leeuw, Marcel: employee of MRM Health Shareholder of MRM Health Possemiers, Sam: Paid consultant of MRM Health Shareholder of MRM Health Haazen, Ludo: Paid consultant for MRM Health Shareholder of MRM Health Vermeire, Séverine: financial support for research from AbbVie, J &amp; J, Pfizer, Takeda and Galapagos speakers’ and/or consultancy fees from AbbVie, Abivax, AbolerISPharma, AgomAb, Alimentiv, Arena Pharmaceuticals, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cytoki Pharma, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, GSK, Hospira, Imidomics, Janssen, J&amp;J, Lilly, Materia Prima, Mestag Therapeutics, MiroBio, Morphic, MRM Health, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Surrozen, Takeda, Theravance, Tillots Pharma AG, VectivBio, Ventyx, Zealand Pharma.

Abstract Background Endoscopic healing is an important treatment goal in Crohn’s disease (CD), in line with European Crohn’s and Colitis Organisation CD guidelines, as it is associated with improved long-term disease outcomes. We assessed the relationship between endoscopic healing and long-term clinical outcomes, patient-reported outcomes (PROs) and hospitalisations in patients (pts) with moderately to severely active CD receiving upadacitinib (UPA) maintenance treatment in the U-ENDURE long-term extension (LTE) study. Methods Pts completing the 52-week U-ENDURE maintenance study were eligible to participate in the LTE study, continuing their previously assigned maintenance treatment. Pts receiving UPA 15 mg or 30 mg once daily in LTE were included in this analysis. Clinical remission based on CD activity index (CDAI &amp;lt;150), CDAI response (≥100-point decrease in CDAI from induction baseline), clinical remission based on stool frequency/abdominal pain (SF/AP) score (average daily soft or liquid SF ≤ 2.8 and average daily AP ≤ 1.0, and neither greater than induction baseline), Inflammatory Bowel Disease Questionnaire (IBDQ) response (≥16-point increase in total IBDQ score from induction baseline) and remission (IBDQ total score ≥170 points), Functional Assessment of Chronic Illness Therapy – Fatigue Scale (FACIT-F) response (≥9-point increase from induction baseline), and economic outcomes (CD-related hospitalisations or surgeries) were evaluated at LTE week 96. Outcomes were compared between pts who achieved vs those who did not achieve endoscopic response, endoscopic remission, or ulcer-free endoscopy (endoscopic outcomes defined in Table footnote) at maintenance week 52 using chi-square testing (nominal P values). Pts with missing outcomes at LTE week 96 were imputed as nonresponders. Results Of 244 pts, 153/244 (62.7%), 112/244 (45.9%) and 89/242 (36.8%) achieved endoscopic response, endoscopic remission, and ulcer-free endoscopy, respectively, at LTE week 0. Significantly (all nominal P≤0.05) more pts who achieved endoscopic response, endoscopic remission or had an ulcer-free endoscopy at LTE Week 0 achieved CDAI response, CDAI remission, SF/AP clinical remission, IBDQ response, IBDQ remission and FACIT-F response at LTE week 96 (Table). CD-related hospitalisations or surgeries at LTE week 96, were significantly (nominal P≤0.05) lower in pts with endoscopic remission and ulcer-free endoscopy at LTE week 0, and numerically lower in pts with endoscopic response. Conclusion A significantly higher proportion of pts who achieved endoscopic outcomes at 52 weeks and received up to 3 years of UPA maintenance treatment achieved long-term improvements in clinical and PROs and reduced CD-related hospitalisations or surgeries. Conflict of interest: Loftus, Jr, Edward: Edward V. Loftus, Jr. has received consulting fees from AbbVie, Abivax, Astellas, Avalo Therapeutics, Biocon, BMS, Celltrion Healthcare, Eli Lilly, Fresenius Kabi, Genentech, Gilead, Iota Biosciences, Iterative Health, Janssen, Merck, Morphic Therapeutics, Ono Pharma, Spyre Therapeutics, Takeda, and TR1X Bio has received research support from AbbVie, Genentech, Gilead, Janssen, Merck, and Takeda and holds stock in Exact Sciences and Moderna. Louis, Edouard: Education and Reserach Grants for my department: Abbvie, Takeda, Johnson and Johnson, Pfizer, Fresenius-Kabi, Celltrion, EG pharma, Sandoz, Falk Personal Fees for conferences, advisory boards and consultancy: Abbvie, Takeda, Ferring, Pfizer, Johnson and Johnson, Lilly, Galapagos, Celltrion, Arena, BMS, Falk, Biokuris, Fresenius-Kabi, Thabor Bossuyt, Peter: Grant support for research from AbbVie, EG Consulting fee from AbbVie, Bristol Meyers Squibb, CIRC, Galapagos, Janssen, Jeito capital, Lilly, Pentax, Pfizer, PSI-CRO, Roche, Takeda, Tetrameros Speakers fee from AbbVie, AMC ICP, Amgen, Bristol Myers Squibb, Celltrion, Dr Falk Benelux, EG, Galapagos, Globalport, Lilly, Medtalks, Materia Prima, Pentax, Springer Media Joshi, Namita: Namita Joshi is a full-time employees/contractor of AbbVie and may own AbbVie stock or options. Shukla, Nidhi: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Dubcenco, Elena: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Aponte, Fernando: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Perkovic, Ashley: Full-time employee/contractor of AbbVie and may own AbbVie stock or options. Panés, Julián: Personal Fees: J. Panés received consultancy fees/honorarium from AbbVie, Alimentiv, Boehringer Ingelheim, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Nimbus, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Sanofi, Sorriso, Spyre Therapeutics, Surrozen, Takeda, and Wasserman, and has served on data safety monitoring boards for Alimentiv, Mirum, Roche, Sorriso, Sanofi, and Surrozen

Abstract Background Clinical remission and endoscopic healing are long-term treatment targets for ulcerative colitis (UC).1 U-ACTIVATE is an ongoing phase 3 long-term extension (LTE) study evaluating the efficacy and safety of upadacitinib (UPA),2 an oral, selective Janus kinase inhibitor approved for adults with moderately to severely active UC.3 Methods This interim analysis of the U-ACTIVATE LTE (NCT03006068) includes patients who responded to 8 weeks of UPA 45 mg once daily (QD) induction therapy and were then rerandomized to placebo (PBO), UPA 15 mg QD (UPA15), or UPA 30 mg QD (UPA30) for 52 weeks of maintenance therapy. Patients who completed maintenance, enrolled in the LTE and were assessed for an additional 192 weeks (total ∼ 5 years). At week 52 of maintenance, patients in clinical remission per adapted Mayo score entered the LTE and received open-label treatment. Nonremitters were eligible for blinded dose escalation in the LTE from maintenance PBO to UPA15 or from maintenance UPA15 to UPA30. Those who received maintenance UPA30 continued blinded UPA30. The study was not designed to compare UPA15 and UPA30 doses. Clinical remission per adapted Mayo score and partial Mayo score, maintenance of clinical remission per adapted Mayo score, achievement and maintenance of endoscopic improvement, and achievement and maintenance of endoscopic remission were assessed in this analysis at LTE week 192 as observed (AO) and by modified non-responder imputation (mNRI). Safety outcomes were treatment-emergent adverse events (TEAEs), presented as exposure-adjusted event rates (EAERs); cut-off date: June 30, 2025. Results In the AO analysis, most patients (&amp;gt; 69%) in both UPA treatment groups achieved clinical remission per adapted Mayo score and per partial Mayo score at LTE week 192 (Table 1). Of the patients in clinical remission per adapted Mayo score at LTE week 0, &amp;gt; 80% maintained remission at LTE week 192 for both UPA doses. Most patients (&amp;gt; 80%) also achieved endoscopic improvement and maintained endoscopic improvement for both UPA doses. Endoscopic remission was achieved by &amp;gt; 50% of patients at LTE week 192 for both UPA doses; 54% (UPA15) and 80% (UPA30) of remitters at LTE week 0 maintained remission at LTE week 192. The mNRI analysis also showed achievement and maintenance of efficacy outcomes (Table 1). EAERs for any TEAEs, serious TEAEs, and TEAEs that led to discontinuation were similar for both UPA doses (Table 2) and were consistent with previous analyses.2,4 Conclusion In the U-ACTIVATE OLE, UPA showed sustained clinical remission and endoscopic improvement at 5 years of treatment. The long-term safety profile of UPA was consistent with previous analyses. This analysis continues to support long-term UPA use in patients with UC.

Abstract Background Data on the association between vedolizumab (VDZ) trough levels (VTLs) and clinical, biochemical, and endoscopic outcomes in Asian patients with inflammatory bowel disease (IBD) are limited. Methods We assessed clinical outcomes, biochemical response using faecal calprotectin (BioRES[FC]) or C-reactive protein (BioRES[CRP]), and endoscopic healing (EH) at weeks 14 (W14) and W54 together with drug optimisation during maintenance therapy among 67 patients treated with VDZ (28 ulcerative colitis [UC] and 39 Crohn’s disease [CD]). Serum VTLs were checked before infusion at W2, W6, W14, and W54 among the patients who maintained VDZ therapy. Associations between early VTLs and outcomes were assessed, with VTL cut-offs proposed using the area under the receiver operating curve (AUC). Results 1) UC: VTL at W2 was significantly higher among W14 corticosteroid-free clinical response (CSF-CRES) achievers vs. non-achievers (43.1 vs. 34.4 μg/mL, P = 0.034) (Figure 1). Patients who achieved W14 BioRES[FC] had higher VTLs at W2, W6, and W14 compared to non-achievers. VTLs at W2 and W6 were significantly higher among patients who achieved W14 EH (42.4 vs. 31.2 μg/mL, P = 0.040 at W2, and 41.6 vs. 28.7 μg/mL, P = 0.035 at W6). The cut-off value of W2 VTL to predict W14 CSF-CREM was 41.0 μg/mL, with an AUC of 0.810 (95% CI, 0.604–1.000). The optimal VTL cut-offs at W2, W6 and W14 associated with W14 BioRES[FC] were 41.0 μg/mL with an AUC of 0.815 (95% CI, 0.636–0.994), 31.3 μg/mL with an AUC of 0.874 (95% CI, 0.733–1.000), and 9.8 μg/mL with an AUC of 0.849 (95% CI, 0.692–1.000), respectively. The predictive VTL cut-offs associated with W14 EH were 41.0 μg/mL with an AUC of 0.739 (95% CI, 0.527–0.951) at W2 and 38.1 μg/mL with an AUC of 0.744 (95% CI, 0.540–0.949) at W6. 2) CD: Higher VTLs at W6 and W14 were observed in those who achieved W14 BioRES[CRP] (Figure 2). Additionally, VTL at W14 was significantly higher among those who achieved W54 BioRES[FC] compared to non-responders (11.2 vs. 3.8 μg/mL, P = 0.036). VTLs at W14 were significantly lower in those who required drug optimisation compared to those who did not (2.2 vs. 5.8 μg/mL, P = 0.004). The optimal VTL cut-offs for predicting W14 BioRES[CRP] were 19.1 μg/mL at W6 and 4.4 μg/mL at W14, with corresponding AUC values of 0.733 (95% CI, 0.539–0.928) and 0.739 (95% CI, 0.539–0.948), respectively. The optimal VTL cut-off for predicting W54 BioRES[FC] was 5.3 μg/mL at W14, with an AUC of 0.859 (95% CI, 0.730–0.988). The optimal VTL cut-offs to predict drug optimisation was 4.6 μg/mL at W14, with an AUC of 0.765 (95% CI, 0.613–0.917). Conclusion This real-life study suggests higher early VTLs correlated with better outcomes, with W14 VTLs potentially predicting long-term outcomes in CD patients. Conflict of interest: Prof. Dr. Ye, Byong Duk: Byong Duk Ye reports consulting fees from AbbVie Korea, BMS Pharmaceutical Korea Ltd., Celltrion, Chong Kun Dang Pharm, CJ Red BIO, Curacle, Daewoong Pharm, Dong-A ST, Ferring Korea, Hanmi Pharmaceutical, Imscout, IQVIA, Johnson &amp; Johnson, Johnson &amp; Johnson Korea, Jeil Pharmaceutical Co., Kangstem Biotech, Korea Otsuka Pharm, Korea United Pharm, Lilly Korea, Medtronic Korea, NanoEntek, ORGANOIDSCIENCES Ltd., Pfizer Korea, Samsung Bioepis, Takeda, Takeda Korea and Yuhan speaker fees from AbbVie Korea, BMS Pharmaceutical Korea Ltd., Celltrion, Cornerstones Health, Curacle, Daewoong Pharm, Eisai Korea, Ferring Korea, IQVIA, Johnson &amp; Johnson Korea, Pfizer Korea, Samsung Bioepis, and Takeda Korea and research support from Celltrion and Pfizer Korea. Kim, Kyuwon: No conflict of interest Yoon, Aran: No conflict of interest Hong, Seung Wook: No conflict of interest Hwang, Sung Wook: no conflicts Park, Sang Hyoung: No conflicts Yang, Dong-Hoon: No conflict of interest Byeon, Jeong-Sik: Clinical study grants from Olympus Co, GC genome, Pharmbio Korea Inc, and Taejoon Pharm. Clinical studies related to the grants include artificial intelligence endoscopy for colon polyp detection/diagnosis, cfDNA for colorectal cancer screening, and colonoscopy bowel preparation. I am a medical advisor of AINEX corporation, Korea, which is an AI endoscopy company. Myung, Seung-Jae: No conflict of interest

Abstract Background Infiltration of neutrophils into intestinal tissue is a crucial component of the inflammatory response in Crohn’s disease (CD). CPa9-HNE, a calprotectin fragment released by human neutrophil elastase during NETosis, has been shown to strongly correlate with endoscopic disease activity in adults with inflammatory bowel disease (IBD) and serves as an indicator of pharmacodynamic response. We aimed to investigate the association of CPa9-HNE with endoscopic disease activity and transmural healing in patients with pediatric CD. Methods The cohort included 174 children with CD (aged 2-18 years, 56% male) who underwent MRE and ileocolonoscopy as part of the ImageKids study (NCT01881490) with serum drawn at enrolment. Age- and sex-matched healthy subjects (HS) were included (n = 82). CPa9-HNE, a human neutrophil elastase-derived fragment of calprotectin, was measured in serum by ELISA. Endoscopic disease activity was graded using the SES-CD score, and radiologic inflammation was assessed by MRE using the radiologist global assessment (RGA) of inflammation recorded on a 0–100 mm visual analog scale (VAS). Transmural healing was defined as endoscopic healing (SES-CD&amp;lt;3, EH) and RGA&amp;lt;10 mm. Spearman’s rho correlations and one-way ANOVA with Dunn’s correction were applied. Results CPa9-HNE showed a fair correlation with the SES-CD score (ρ = 0.30, p &amp;lt; 0.001). A positive correlation was also observed between CPa9-HNE and RGA of inflammation (ρ = 0.30, p &amp;lt; 0.001). For SES-CD, CPa9-HNE was significantly elevated in all subgroups compared with HS (p &amp;lt; 0.0001 for all) and demonstrated a stepwise increase across disease severity groups (fig. 1A). Patients with severe endoscopic disease had significantly higher levels of CPa9-HNE than those in remission (ng/ml [IQR]: 275.6 [182.4-461.9] vs. 158.1 [127.6-211.2], p &amp;lt; 0.05) (fig. 1A). CPa9-HNE was able to significantly discern patients with transmural healing from patients with transmural disease activity (fig. 1B) (AUC [95%CI]: 0.77 [0.67-0.86]). Conclusion This study showed that CPa9-HNE, a biomarker of neutrophil activity, is associated with mucosal and radiologic inflammation in pediatric CD. These findings highlight the potential use of CPa9-HNE as a complementary tool for the endoscopic or radiographic assessment of intestinal inflammation and provide an opportunity for further studies in children with CD. Conflict of interest: Dr. Mortensen, Joachim: Fulltime employee and shareholder at Nordic Bioscience A/S Focht, Gili: No conflict of interest Sorokina Alexdóttir, Marta: Fulltime employee at Nordic Bioscience A/S Quteineh, Ahmad: No conflict of interest Pehrsson, Martin: Fulltime employee at Nordic Bioscience A/S Griffiths, Anne: Grant: Abbvie Personal Fees: Abbvie, Alfasigma, Amgen, Janssen, Lilly, Merck, Pfizer, Roche, Takeda Church, Peter Christopher: No conflict of interest baldassano, Robert N.: No conflict of interest Silverstein, Jared: No conflict of interest Bay-Jensen, Anne-Christine: Fulltime employee and shareholder at Nordic Bioscience A/S Karsdal, Morten Asser: Fulltime employee and shareholder at Nordic Bioscience A/S Turner, Dan: Consultation fee: Janssen, Pfizer, Ferring, Abbvie, Takeda, Prometheus Biosciences, Lilly, SorrisoPharma, Boehringer Ingelheim, Galapagos, BMS, AlfaSigma, Merck, Gentech Research support: Janssen, Abbvie, Takeda, Pfizer Royalties: Shaare Zedek Medical Center, Hospital for Sick Children