ABSTRACT Project LIVE (Love, Inclusivity, Values, and Education) is a five-year Centers for Disease Control and Prevention (CDC) funded project designed to evaluate the effectiveness of a school-based curriculum aimed at preventing the sexual exploitation of children (SEC) utilizing community-based participatory action research (CBPAR) methods. This paper describes challenges, successes, and lessons learned throughout the first two years of the project (Phase I), encompassing the open pilot trial. Framed by ecological systems theory (EST);, primary challenges at the microsystem (e.g. fictitious people trying to enroll in the study, difficulty matching anonymous surveys across time), mesosystem (e.g. misalignment across microsystems, differences in cultural and lived experience background between student participants and the research team, student resistance to participation), exosystem (e.g. personnel turnover), and macrosystem (e.g. state law changes requiring active guardian consent) are delineated. Active participation among research advisory board members, protocol adaptability, and collaboration and support across microsystems constitute major successes from Phase I.

This article reports on the workshop “Literary Translation and (Translation) Technology considered from Research, Practice and Legal Perspectives”, which took place at the XXII KäTu Symposium on Translation and Interpreting Studies on 12 April 2025 at the University of Helsinki. It was organized by the project Narrative Text, Translator and Machine (University of Turku, 2022–2026), funded by the Research Council of Finland. The aim was to share knowledge on recent research on technology-assisted literary translation and to engage in a dialogue with professionals. The workshop opened with three papers, by Claudine Borg (University of Malta), Lauri Niskanen (University of Turku), and Maarit Koponen (University of Eastern Finland). The second part consisted of a panel discussion. The speakers were translators Jaakko Kankaanpää and Riina Vuokko from the Literary Translators’ Branch of the Union of Journalists in Finland, translator Nina Mäki-Kihniä, who is an advisory board member of the Narrative Text project, and Niina Vettensola, LL.M., who is the Executive Director of Sanasto, the Finnish literary copyright society.

Research methodology The information provided in this case was gathered by the author through interviews with several board members who serve on a non-profit foundation board. To ensure confidentiality, all names in the case have been disguised, along with the organization’s name, associated industry, location, exact value of the fundraising campaign and dollar value of the significant donation from the board chair at that time. However, all other elements of the case (including the history of the organization, governance structure, potential governance challenges and ratio of the major gift to the total value of the fundraising campaign) are factual and have not been exaggerated or changed in any way. Secondary research was also conducted on best practices in non-profit governance. An earlier version of the case was presented at the North American Case Research Association Conference in Orlando, Florida in October 2024. Feedback from peer reviewers informed improvements to the case and teaching note. Case overview/synopsis Sheila Chen is a board member and former board chair of the Golden Oaks Hospital Foundation (GOH Foundation) in Oakville, Ontario, Canada. In 2024, an issue was raised at a board meeting regarding chief executive officer (CEO) Nina Rahman’s decision to pay cash bonuses to staff – including one union member – out of her personal funds. While well-intentioned, this action raised concerns about boundaries, authority and influence, prompting Chen to examine broader governance issues, including the CEO’s relationship with Robert Blackwell, a major donor and advisory board member who has become increasingly involved in board affairs. As a member of the governance committee and past board chair, Chen has taken responsibility for ensuring these governance challenges are addressed and that a plan is developed to strengthen oversight and clarify roles. This case invites students to explore how well-intentioned actions can create governance risks when they blur boundaries between personal generosity, organizational policy and board oversight. It challenges students to identify potential issues arising from board dynamics and power imbalances and to develop practical solutions and an action plan for governance reform. Complexity academic level This case is suitable for use in graduate-level courses in corporate governance, governance and leadership or non-profit management. It can be used in both in-person and synchronous online courses.

BackgroundThe National Emergency Airway Registry for Pediatric Emergency Medicine (NEAR4PEM) developed an evidence-based pre-intubation checklist, however its successful integration to clinical practice in the Pediatric Emergency Department (PED) requires attention to implementation. Given the complex conditions influencing checklist use, it is essential to work with key informants to understand multilevel determinants and identify the most effective strategies for implementation. The objective of this study was to systematically identify barriers to checklist adoption and to prioritize and detail targeted strategies as an implementation blueprint to support successful checklist integration into clinical practice.MethodsNEAR4PEM recruited Airway Champion (AC) teams composed of physicians, nurses, pharmacists, and respiratory therapists at each PED. Our methodology consisted of a five-step modified conjoint analysis. In Step 1, a mixed-methods formative evaluation was conducted, utilizing focus groups and surveys for identification of barriers and facilitators to checklist implementation. In Step 2, key informants prioritized the identified barriers according to feasibility and impact quantitatively via survey. In Step 3, the prioritized barriers were matched with implementation strategies from a published compilation (Expert Recommendations for Implementation Change, ERIC) via virtual facilitated sessions. In Step 4, these strategies were ranked for feasibility and impact by Advisory Board (AB) members. In step 5, the AB detailed the prioritized implementation strategies in an implementation blueprint.ResultsIn Step 1, ACs from 13 sites completed 45 surveys, which, together with focus groups, identified 16 unique barriers. For Step 2, these key informants prioritized 6 barriers of high impact and high feasibility. For Step 3, an implementation science team assisted ACs with selection of 24 ERIC strategies. In Steps 4 and 5, the AB prioritized 19 ERIC strategies and incorporated them into an implementation blueprint, detailing how each could be applied across different phases to guide future airway teams.ConclusionsAn implementation blueprint for a PED pre-intubation checklist was collaboratively developed with interprofessional AC team members and implementation scientists. This blueprint includes a manageable set of prioritized barriers and detailed strategies to navigate the implementation process. Future steps involve implementation of the checklist with concurrent evaluation of implementation and patient outcomes.

BackgroundParticipant recruitment and retention are major concerns for research teams and can influence study success and relevance of findings. Known challenges include access to relevant populations, mistrust, fear, lack of awareness of research, sociocultural considerations, complexity of studies, burden, literacy, and language barriers.Community Engaged (CE) Research builds sustainable community‐researcher partnerships to advance science through co‐ownership and co‐creation of research and has gained attention. To this end, the Recruitment and Retention of Alzheimer's Disease Diversity Genetic Cohorts in the Alzheimer's Disease Sequencing Project (READD‐ADSP) includes a CE Core to increase awareness of Alzheimer's disease and related dementias (ADRD) and brain health and promote participation in ADRD research across the Africa.MethodsStandard Operating Procedures based on CE principles were developed to guide equitable engagement and responsibilities for study team and Community Advisory Board (CAB) members across nine African Dementia Consortium (AfDC) countries.Efforts included annual training on study objectives, progress reports, relevant clinical and research topics, community needs and recommendations, and goals. Partnerships were leveraged to increase brain health, dementia, and research awareness, promote recruitment and retention, and co‐create educational resources. CAB members shared expertise on their communities via focus groups (FGs) and standing meetings.ResultsEstablished 21 CABs comprised of 141 community members across sites. Membership included community and faith leaders, public health professionals, caregivers, and NGO representatives, among others. Partnerships resulted in increased recruitment (e.g., over 50% of participants in Ibadan were from CE efforts). Co‐led community awareness campaigns and outreach efforts were conducted across study regions to maximize reach (e.g., community health screenings, educational promotion via pamphlets, social media, podcasts, caregiver video narratives, and dance classes). Following year 2 training, CAB members (n = 83) participated in FGs (n = 10). Major themes identified were prevailing misconceptions on dementia, stigma, and the need for culturally tailored information.ConclusionAdoption of CE strategies, most notably our CAB partnerships, has ensured successful study recruitment, retention, and awareness of dementia. Co‐created resources and outreach efforts promoted a collaborative, equitable approach to brain health awareness and dementia research and in Africa. While time intensive, CE can strengthen collaborative research and community needs and priorities.

Abstract Background Transperineal ultrasound (TPUS) is increasingly used to assess distal rectal inflammation and perianal complications in inflammatory bowel disease (IBD). However, indications, technical protocols, activity thresholds, and response criteria remain heterogeneous across centres. This study aimed to develop an international expert consensus on the clinical role, standardised technique, and reporting framework for TPUS in IBD. Methods An international multidisciplinary panel of TPUS, intestinal ultrasound, and IBD experts participated in a structured Delphi process. Two online voting rounds were followed by iterative refinement of statements. Panellists rated agreement on a 5-point Likert scale and assigned evidence levels (high/moderate/low) based on the published literature and expert experience. A priori, consensus was defined as ≥ 80% of respondents voting “agree” or “strongly agree”. Participants were allowed to abstain from voting on any statement. Statements that did not reach consensus were revised or discarded. Results In total, 40 experts from Europe, Asia, North America, and Oceania completed ≥1 voting round. Overall, >30 statements across 19 domains achieved consensus (see Table). Key domains included: (i) clinical role of TPUS in ulcerative colitis (UC), pouchitis, and perianal disease in Crohn’s disease (pCD); (ii) standardisation of probe choice, preparation, and patient positioning; (iii) required scan planes by indication; (iv) orientation conventions and rectal bowel wall thickness (BWT) measurement; (v) Doppler settings for low-flow detection; (vi) TPUS activity thresholds and remission definitions for rectal UC (including adult and paediatric cut-offs); (vii) classification and reporting of pCD (Parks/AGA ± TOpClass); (viii) integration with MRI/TRUS; (ix) pragmatic follow-up schedules; and (x) minimum reporting datasets and safety triggers. Most final statements reached ≥90% agreement, while evidence levels ranged from low (technical parameters, follow-up cadence) to high (classification frameworks, MRI indications). Conclusion This international Delphi process provides comprehensive expert consensus on TPUS in IBD, defining its clinical role and standardising core technical, interpretive, and reporting elements. These statements offer a practical framework for implementing TPUS in routine care and mulicentre studies. Conflict of interest: Sagami, Shintaro: Shintaro Sagami has served as an advisory board member, consultant, or speaker for AbbVie, Alimentiv, Bristol Myers Squibb, Celltrion, EA Pharma, Eli Lilly, Ferring Pharmaceuticals, Gilead Sciences, Janssen Pharmaceuticals, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda, and Zeria Pharmaceutical, and has received research funding from Bristol Myers Squibb, EA Pharma, Gilead Sciences, Helmsley Charitable Trust, JIMRO, Kyorin Pharmaceutical, Miyarisan, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Sekisui Medical, Samsung, Takeda, and Zeria Pharmaceutical. Verstockt, Bram: Shintaro Sagami has served as an advisory board member, consultant, or speaker for AbbVie, Alimentiv, Bristol Myers Squibb, Celltrion, EA Pharma, Eli Lilly, Ferring Pharmaceuticals, Gilead Sciences, Janssen Pharmaceuticals, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda, and Zeria Pharmaceutical, and has received research funding from Bristol Myers Squibb, EA Pharma, Gilead Sciences, Helmsley Charitable Trust, JIMRO, Kyorin Pharmaceutical, Miyarisan, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Sekisui Medical, Samsung, Takeda, and Zeria Pharmaceutical. Allocca, Mariangela: Personal Fees: consulting fees from Nikkiso Europe, Mundipharma, Janssen, Abbvie, Pfizer, Ferring, Galapagos, Sandoz, Lilly and Alfasigma Pal, Partha: ​Partha Pal received consultancy fees/speaker honorarium from Johnson and Johnson, Takeda Pharmaceutical Company, Cipla Ltd, Sun Pharma, Zydus Biosciences, Dr Reddy Labs, Abbott India, RPG Life sciences, La Renon Healthcare Pvt Ltd and Daewoong Pharma Dal Buono, Arianna: No conflict of interest Christensen, Britt: No conflict of interest Albshesh, Ahmad: No conflict of interest Carter, Dan: No conflict of interest Lu, Cathy: No conflict of interest de Voogd, Floris: No conflict of interest Fraquelli, Mirella: No conflict of interest Seidelin, Jakob Benedict: No conflict of interest Blunt, Heather: No conflict of interest Vitale, Elaina: No conflict of interest Winter, Michael: No conflict of interest

Abstract Background Inflammatory Bowel Disease (IBD), including Ulcerative Colitis (UC) and Crohn’s Disease (CD), are chronic, incurable conditions with a variable course that significantly affect patients’ quality of life. This unpredictable trajectory—characterized by periods of remission, relapse, or continuous activity—significantly impacts psychological, social, familial, and professional aspects. Therefore, considering the patient’s perception is essential for preventing complications and improving overall well-being. Methods This was an observational, analytical study that included 26 postsurgical patients diagnosed with IBD. Demographic and clinical variables, along with quality of life aspects, were evaluated. These quality of life domains (abdominal pain, bowel movement frequency, social life, work and education, sleep, energy, emotions, body image, sexual function and joint pain) were scored from 0 to 10 based on patient perception. Descriptive statistics were performed and the Mann-Whitney U test was applied using IBM SPSS Statistics v26. Results Out of 26 total patients, 69.2% had Crohn’s Disease (CD) and 30.8% had Ulcerative Colitis (UC). 53.8% were male and 46.2% were female. The mean age was 46 years (UC: 39 years; CD: 49 years). Regarding procedures: 42.3% (n = 11) underwent perianal surgery (3 UC, 8 CD); 30.8% underwent intestinal resection with primary anastomosis (2 UC, 6 CD); 26.9% underwent diversionary intestinal surgery (3 UC, 4 CD). In terms of pharmacological treatment, 76.9% were on advanced therapy. Advanced therapy use was higher in CD patients (83.3%) than in UC patients (62.5%). A statistically significant difference was identified in the work and education domain between patients with diversionary intestinal surgery and those with primary anastomosis surgery (p = 0.009) and in the energy domain between the groups with primary anastomosis and perianal surgery (p = 0.041). Conclusion In this sample, postsurgical IBD patients were predominantly male, though females were the majority within the CD subgroup. Perianal surgery was the most frequent procedure, followed by intestinal resection with primary anastomosis. IBD negatively impacts quality of life across all assessed domains. The surgical groups were largely similar, with no significant differences found, except for the impact on professional activity (diversion vs. anastomosis) and energy (anastomosis vs. perianal). These differences suggest that the very act of surgical intervention, regardless of type, profoundly affects patient quality of life. These findings underscore the critical need for timely interventions both pre and post surgery and highlight the importance of a multidisciplinary team to provide comprehensive support throughout the patient’s disease course. Conflict of interest: Rosales, Paola: No conflict of interest Gonzalez, Emmanuel: No conflict of interest Chida, Jesus: No conflict of interest Contreras Aviles, Estefania: No conflict of interest Hernandez, Victor: No conflict of interest Rodriguez, Hector: No conflict of interest Sebastian, Valeria: No conflict of interest Lopez, Yazmin: No conflict of interest Jimenez, Billy: No conflict of interest Dr. De Leon Rendon, Jorge Luis: Member of Advisory Boards, key opinion leader, and speaker for Abbvie Mexico, Takeda Mexico, and Janssen Mexico. He has served as a key opinion leader and lecturer for Schwabe Pharma Mexico, Servier, Pfizer, Alfasigma, and Siegfried Rhein Mexico. He has received support for research manuscript publication and editing from Takeda and Schwabe Pharma Mexico. Additionally, he has coordinated research studies and medical education programs with Shire, Bristol Myers Squibb, Takeda, Schwabe Pharma, Abbvie, Janssen, MSD, and Roche.

Abstract Background Inflammatory bowel disease (IBD), which includes chronic idiopathic Ulcerative Colitis (UC) and Crohn’s disease (CD), is associated with a higher risk of infections, especially in patients under immunosuppressive treatment. Vaccination is a key tool in prevention but its coverage and awareness in our population remains limited. There is little known data in Mexico regarding access, perception and barriers related to immunization. Evaluating these aspects is essential to improve preventive care in specialized clinics and to strengthen institutional vaccination strategies. Methods Observational, analytical, and cross-sectional study. Fifty-nine patients with a confirmed diagnosis of UC or CD, who were under active follow-up and regularly attending outpatient consultations, were included. All agreed to participate through the application of a structured survey. The instrument collected information on vaccination history, knowledge regarding special schedules, and identification of barriers to immunization. Statistical analysis was performed with SPSS v29.0. Frequencies and proportions were used for qualitative variables, and chi-square or Fisher’s exact test was applied for group comparisons, considering a p value < 0.05 as statistically significant. Results Fifty-nine patients with IBD were surveyed, of whom 62.7% had UC and 37.3% CD. Only 52.5% reported having a complete vaccination schedule, while 33.9% were unaware of their status. Only 20.3% reported having a vaccination card. More than half (55.9%) had received at least one vaccine after their IBD diagnosis, mainly against COVID-19 (91.5%) and influenza (66.1%). Regarding knowledge, only 23.7% were aware of the existence of a special schedule for immunosuppressed patients. The main barriers identified were lack of information (84.7%), absence of medical recommendations (25.4%). Nevertheless, 89.8% of participants considered vaccination to be very important, and 74.5% recognized its effectiveness in preventing severe infections. No statistically significant differences were found between UC and CD patients in most of the variables, except for vaccination against herpes zoster, which was more frequent in CD patients (p = 0.029). Conclusion Vaccination coverage in IBD patients treated at our center is suboptimal, with significant gaps in knowledge and medical guidance regarding special schedules for immunosuppressed patients. Although most patients acknowledge the importance of immunization, obstacles persist such as lack of information and limited medical recommendations. These findings highlight the need to implement educational strategies and institutional protocols that reinforce systematic immunization as an integral part of the follow-up of patients with IBD. Conflict of interest: Rosales, Paola: No conflict of interest Gonzalez, Emmanuel: No conflict of interest Chida, Jesus: No conflict of interest Hernandez, Victor: No conflict of interest Rodriguez, Hector: No conflict of interest Sebastian, Valeria: No conflict of interest Contreras Aviles, Estefania: No conflict of interest Lopez, Yazmin: No conflict of interest Jimenez, Billy: No conflict of interest Dr. De Leon Rendon, Jorge Luis: Dr. Jorge Luis De León Rendón is a member of Advisory Boards, key opinion leader, and speaker for Abbvie Mexico, Takeda Mexico, and Janssen Mexico. He has served as a key opinion leader and lecturer for Schwabe Pharma Mexico, Servier, Pfizer, Alfasigma, and Siegfried Rhein Mexico. He has received support for research manuscript publication and editing from Takeda and Schwabe Pharma Mexico. Additionally, he has coordinated research studies and medical education programs with Shire, Bristol Myers Squibb, Takeda, Schwabe Pharma, Abbvie, Janssen, MSD, and Roche.

Abstract Background Inflammatory Bowel Disease (IBD) affects young individuals, with an incidence peak between the ages of 15 and 40, coinciding with the female reproductive period. The clinical, therapeutic, and reproductive implications for women of childbearing age with IBD are significant, due to the potential impact of the disease and the risks associated with treatment, surgery, and pregnancy. There is scarce regional information regarding the gynaecological and obstetric characteristics and their relationship with the clinical and therapeutic phenotype of the disease in Latin American populations. A detailed characterisation of these patients in tertiary referral centres can contribute to optimizing comprehensive care strategies and safe reproductive planning for women. Methods A cross-sectional, observational and analytical study was carried out at the IBD Clinic of the General Hospital of Mexico. Women of childbearing age (15 to 49 years) with a confirmed diagnosis of IBD, in active follow-up between March 2023 and June 2025, were included. Clinical, demographic, and gynaecological and obstetric data were obtained through direct interviews. Statistical analysis was performed using IBM SPSS v. 29. Quantitative variables were compared using the independent samples Student’s t-test. For qualitative variables, chi-squared tests or Fisher’s exact test were employed. A p value of 0.05 was considered statistically significant. Results Of a cohort of 298 IBD patients in active follow-up, 61 (20.5%) corresponded to women of childbearing age; 50 patients (82.0%) had Ulcerative Colitis (UC) and 11 (18.0%) had Crohn’s Disease (CD). In the UC group, the most common presentation was pancolitis (70.0%), whereas in the CD group, stenosing behaviour (54.5%) and ileocolonic location (36.4%) predominated. The need for surgery was more frequent in CD patients (45.5%). Specifically, right hemicolectomy was exclusive to the CD group (p = 0.031). No significant differences were identified between both groups concerning age, reproductive variables, extraintestinal manifestations or the presence of stoma. The proportion of patients who had prenatal counselling was 42.6%, with no statistically significant difference between the groups. Conclusion In this cohort, 20.5% of IBD patients in active follow-up were women of childbearing age. Clinical and therapeutic differences between UC and CD were identified, highlighting the higher frequency of pancolitis in UC, and of stenosing phenotype and major surgery in CD. Less than half of the patients received prenatal counselling, which underscores the need to reinforce reproductive advice and multidisciplinary approaches in this group. Conflict of interest: Rosales, Paola: No conflict of interest Gonzalez, Emmanuel: No conflict of interest Rodriguez, Hector: No conflict of interest Contreras Aviles, Estefania: No conflict of interest Sebastian, Valeria: No conflict of interest Hernandez, Victor: No conflict of interest Chida, Jesus: No conflict of interest Lopez, Yazmin: No conflict of interest Jimenez, Billy: No conflict of interest Dr. De Leon Rendon, Jorge Luis: Dr. Jorge Luis De León Rendón is a member of Advisory Boards, key opinion leader, and speaker for Abbvie Mexico, Takeda Mexico, and Janssen Mexico. He has served as a key opinion leader and lecturer for Schwabe Pharma Mexico, Servier, Pfizer, Alfasigma, and Siegfried Rhein Mexico. He has received support for research manuscript publication and editing from Takeda and Schwabe Pharma Mexico. Additionally, he has coordinated research studies and medical education programs with Shire, Bristol Myers Squibb, Takeda, Schwabe Pharma, Abbvie, Janssen, MSD, and Roche.

Abstract Background The subcutaneous (SC) formulation of the infliximab (IFX) biosimilar CT-P13 is increasingly used in inflammatory bowel disease (IBD). A direct comparison between patients switched from intravenous (IV) IFX to SC CT-P13 and those who remained on IV IFX may provide valuable insights for clinical practice. Methods The CISI study is a retrospective, observational study conducted at the IBD Unit of “Villa Sofia-Cervello” Hospital, Palermo, Italy. Consecutive adult patients with Crohn’s disease (CD) or ulcerative colitis (UC) in stable, steroid-free clinical remission (Harvey-Bradshaw Index <5 for CD or partial Mayo score <2 for UC, without steroid use for ≥4 months) while on maintenance IV IFX (5 mg/kg every 8 weeks) were included. Two arms were compared. Arm 1: patients in stable, steroid-free remission who were switched from IV IFX to SC CT-P13; Arm 2: patients in stable, steroid-free remission who continued IV IFX. A propensity score-weighted analysis using inverse probability of treatment weighting (IPTW) with stabilized weights was applied to reduce selection bias. The primary endpoint was treatment persistence without steroids. Secondary endpoints included the incidence rate (IR) of adverse events (AEs) and the clinical activity at 6, 12, and 24 months. Results Overall, 251 patients were included (CD: 53.8%, UC: 46.2%): 134 remained on IV IFX and 117 were switched to SC CT-P13. Mean follow-up was 24.7 ± 29.8 months for IV IFX and 20.9 ± 14.9 months for SC CT-P13 (p = 0.41). At month 12, retention rates were 63.6% for IV IFX and 78.5% for SC CT-P13. Kaplan–Meier analysis showed no significant difference (log-rank p = 0.10 – figure 1). In the multivariable Cox model, female sex was independently associated with higher discontinuation risk (HR 2.59; 95% CI 1.66–4.04; p < 0.001). A significant time-dependent effect was detected for the SC CT-P13 (p = 0.005). During the first months after switching, patients on SC CT-P13 showed a higher probability of treatment discontinuation compared with those maintained on IV therapy. However, this excess risk progressively decreased and crossed unity around month 8, after which the likelihood of persistence became higher for SC CT-P13. The AE IR was 6.16 (95% CI 3.59–9.87) per 100 person-years for IV IFX and 4.42 (95% CI 2.02–8.39) for SC CT-P13. The IPTW-adjusted IR ratio (SC/IV) was 0.95 (95% CI 0.38–2.42; p = 0.92). No significant differences between the two arms were observed in HBI, partial Mayo score, or CRP levels at 6, 12, or 24 months. Conclusion Switching from IV IFX to SC CT-P13 demonstrated comparable persistence, safety, and disease control to continued IV therapy in IBD patients with stable remission. In the long term, the SC formulation may be associated with greater treatment persistence. Conflict of interest: Dr. Macaluso, Fabio Salvatore: Advisory board and/or lecture fees for: AbbVie, MSD Galapagos, Sandoz, Takeda, Janssen, Eli-Lilly, Pfizer, Alfasigma, Giuliani Funding: The CISI study is an investigator-initiated study funded through an unrestricted educational grant provided by Celltrion Healtchare Italy s.r.l. Calderone, Silvia: No conflict of interest Renna, Sara: SR served as an advisory board member or received lecture grants from AbbVie, Johnson and Johnson, Pfizer, Alfasigma, Takeda, Eli Lilly. Casà, Angelo: No conflict of interest Orlando, Rosalba: No conflict of interest Orlando, Emanuele: No conflict of interest Li Voti, Raffaele: No conflict of interest Vastarella, Josephine: No conflict of interest Armetta, Samuele: No conflict of interest Morello, Simona: No conflict of interest Orlando, Ambrogio: Advisory board and/or lecture fees for: AbbVie, Galapagos, Celltrion, MAD, Sofar, Pfizer, Takeda, Cadigroup, Sandoz, Janssen, Eli-Lilly, Alfasigma

Abstract Background Elderly-onset inflammatory bowel disease, onset > 60 years of age, constitutes 10-15% of all incident IBD-patients. Elderly onset-IBD patients may be frailer and have more comorbidities compared to adult-onset IBD. The aim of the study was to compare symptoms and clinical presentation in adult onset-IBD patients to elderly onset-IBD patients. Methods The I-SCAN (IBD-Scandinavian cancer in IBD study) cohort includes all patients in Sweden, Norway and parts of Denmark with two ICD-codes for IBD (ICD-9 555, 556, 563.01, 563.10; ICD-10: K50, K51, K52.3) in national registers, 1987-2016 for inpatients and 1997-2016 for outpatients (1986-2018 for Denmark). From this cohort a case-cohort study was empaneled. For cancer cases, n = 2933, and a random sample of the cohort, n = 1279, detailed chart abstraction was done including information on disease behavior, disease extent and macroscopical and microscopical findings from endoscopic procedures. From the random non-cancer sub-cohort, we compared symptoms and clinical presentation in adult-onset IBD patients (18-59 years of age) to elderly onset-IBD patients (≥ 60 years of age). Results In total 1034 patients with IBD diagnosis ≥ 18 years of age were studied, 857 had adult onset-IBD and 177 elderly onset-IBD. No differences were seen between the groups for the distribution of diagnosis. Number of colonoscopies were equal for the first five years of disease, a median of two colonoscopies were conducted among both adult- and elderly onset IBD. Macroscopical inflammation in adult- and elderly onset Crohn’s disease (CD) as well as adult- and elderly onset Ulcerative colitis (UC) did not differ for colonoscopies with clinical indication (p = 0.57). Microscopical inflammation also did not differ between adult onset IBD (no activity 28.6%, mild 16.9%, moderate 23.8%, severe 30.7%) and elderly onset IBD (no activity 26.2%, mild 14.4%, moderate 27.2%, severe 32.2) for the first five years of disease (p = 0.43). In addition we found no differences in symptoms such as diarrhoea, mucus and blood in stools between adult- and elderly onset IBD patients. Patients with adult-onset CD had less anaemia, 7.9%, than elderly-onset UC, 18.8%. Adult-onset UC had less weight loss, 13.9% than elderly-onset UC, 22.2%. Conclusion The clinical presentation of elderly onset-IBD is comparable to that of adult onset-IBD regarding symptoms at diagnosis as well as inflammation on both the macroscopical and microscopical level. Conflict of interest: Dr. Bjorner, Kajsa: Advisory board member for Lilly, Advisory board member Takeda. Högdén, Amanda: Nothing to delclare Perrin, Vera: No conflict of interest Refsum, Erle: No conflict of interest Larsen, Lone: Speaker fee from Takeda, Eli Lilly, Abbvie Share holder Novo Nordisk A/S Advisory Board for Tillotts, Abbvie, Eli Lilly, Celltrion Consultancy for Eli Lilly Erichsen, Rune: No conflict of interest Gantzel, Rasmus Hvidbjerg: No conflict of interest Ye, Weimin: No conflict of interest Jess, Tine: Personal Fees: Consultancy for Ferring, Pfizer, Johnson & Johnson Kalager, Mette: No conflict of interest Thelin Schmidt, Peter: Advisory Board member for Gilead Nordic, Janssen Cilag, and Norgine and as invited speaker for MSD Blom, Johannes: No conflict of interest

Abstract Background Subcutaneous (SC) infliximab (IFX) is available for maintenance treatment of Crohn’s disease (CD) following intravenous induction. In DIRECT-CD, a prospective randomised controlled international trial, CD patients with active disease initially received SC IFX induction at 240 mg at week (W)0 and 2, followed by 120 mg every other week (eow). As early pharmacokinetic data indicated suboptimal IFX exposure, the protocol was amended to a higher first dose (480 mg at W0) for all patients and a doubled maintenance dose (240 mg eow from W4) for patients ≥80 kg. We compared IFX pharmacokinetics between SC IFX with and without immunomodulator (IMM) use across different induction schemes, and in relation to pharmacogenomic profiles. Methods Patients with moderate-to-severe CD (CD activity index >220 and endoscopic ulceration) received SC IFX induction according to either the original regimen (240 mg at W0 and W2, then 120 mg eow) or the amended regimen (480 mg at W0 and 240 mg at W2), followed by weight-based maintenance dosing (120 mg eow for patients <80 kg and 240 mg eow for patients ≥80 kg). Patients were randomized to SC IFX mono- or combination therapy with an IMM (thiopurine or methotrexate). Serum IFX and anti-drug antibodies (ADA) against IFX were measured at W2, 4, 8 and 14. HLA-DQA1*01-06 genotyping was performed at W0. Results Sixty patients were randomized (53% female, median age 30 years, median body weight 70.9kg, 62% ileocolonic disease, 70% non-stricturing/non-penetrating disease, 8% active perianal disease, 72% biologic-naïve). 31/60 patients received the original induction, 50/60 received standard maintenance (120 mg eow), 31/60 patients received a concomitant IMM. Patients receiving 480 mg at W0 had higher serum IFX concentrations at W2, W4, and W8, but not W14, compared to original induction (Figure 1A). No differences in serum IFX concentrations were observed between SC IFX mono- and combination therapy (Figure 1B). Across all time points, ADA against IFX (>12 AU/mL) were detected 15 times in 9 patients; none occurred at W2. At W14, 8 monotherapy patients and 1 combination therapy patient were ADA-positive (P = 0.048). The HLA-DQA1*05 allele (31/60, 52%) was associated with lower serum IFX concentrations and higher ADA levels (P = 0.035). Conclusion In CD patients receiving SC IFX, intensified induction (480-240 mg) resulted in higher early serum concentrations. Combination therapy with IMM did not increase IFX concentrations, yet was associated with a lower proportion of ADA-positive patients at W14. Carriers of HLA-DQ5 showed lower IFX exposure and higher immunogenicity. These data suggest limited added benefit of concomitant IMM for IFX pharmacokinetics during intensified SC IFX induction. Conflict of interest: Anjie, Suzanne: No conflict of interest Jansen, Jeroen Michiel: consultant forJanssen, Galapagos, Takeda en Lilly. Jharap, Bindia: No conflict of interest Mares, Wout: No conflict of interest Duijvestein, Marjolijn: Grant: Speaking fees from Bristol Meyers Squibb, Takeda, Galapagos, Janssen, Dr. Falk, Advisory board fees from Abbvie, Bristol Meyers Squibb, Celltrion, Galapagos Alfasigma, Janssen, Takeda Grant/Research support: Pfizer, Bristol Meyers Squibb, Galapagos, Alfasigma, Janssen, Lilly 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 & Johnson, Johnson & 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 & Johnson Korea, Pfizer Korea, Samsung Bioepis, and Takeda Korea and research support from Celltrion and Pfizer Korea. Kim, Tae Oh: No conflict of interest Kang, Sang-Bum: Sang-Bum Kang has received research grants from Celltrion, Chong Kun Dang Pharm, Il-Yang Pharm, Pharmbio Korea, and Taejoon Pharm consulting fees from AbbVie Korea, Ferring Korea, Janssen Korea, and Takeda Korea and speaking fees from AbbVie Korea, Celltrion, Ferring Korea, Janssen Korea, Pfizer Korea, Taejoon Pharm, and Takeda Korea. Kim, Eun Soo: Eun Soo Kim has acted as a speaker or advisory board member of AbbVie, Celltrion, J&J, Ferring, Pfizer, Samsung Bioepis, and Takeda. Park, Dong Il: Dong Il Park has served as an advisory board member for AbbVie, Celltrion, Ferring, and Shire (a member of the Takeda group of companies). Maljaars, Jeroen: Grants, consulting fees, payment for lectures: Galapagos, abbvie, takeda Römkens, Tessa: No conflict of interest Oldenburg, Bas: Unrestricted grants: Abbvie, Takeda, Pfizer, Galapagos\nAdvisory boards: Abbvie, Takeda, Pfizer, Lilly, Galapagos, Janssen Boukema, Inge: No conflict of interest Janssen, Reimer: No conflict of interest Oldenburg, Lotte: No conflict of interest Van Oostrom, Joep: Other: Speaker fees from Tillott’s and Takeda Van Welsen, Inge: No conflict of interest Clasquin, Esme: No conflict of interest D’Haens, Geert: Grant:Pfizer, BMS, Johnson and Johnson, Abbvie, Alimentiv BV, Eli Lilly, Takeda, Prometheus Laboratories Persona

Abstract Background Intestinal ultrasound (IUS) is increasingly used for real-time assessment of inflammatory bowel disease (IBD) but quantitative analysis with artificial intelligence (AI) remains limited to bowel wall thickness (BWT) and single-frame segmentation, failing to exploit the temporal information in cineloops (CLs). The aim here was to evaluate the accuracy of an AI model compared to expert central readers using IUS CLs. Methods We developed a novel model using a semi-supervised algorithm combined with a temporal module, trained on 680,000 IUS images from 1572 CLs (327 patients from multiple centres). 1205 frames from 403 CLs on 94 patients were labelled by 8 domain experts (203 validation, 1002 training images). The CLs had various segments per patient with active IBD, and included axial, longitudinal and oblique sections. An external test set (27 patients, 58 CLs) of active Crohn’s patients (ascending, transverse, descending colon), centrally read by 3 expert readers, was used for initial evaluation. The model was optimized to segment 9 categories including bowel wall (BW), psoas, iliac vessels (IV), and inflamed mesentery (IM). Each output was based on a current frame and context representations from previous frames. The model continuously segments and tracks anatomy, generating temporally coherent delineations and data that feed intra- and inter-frame measurement algorithms. On the validation set, we calculated the Dice similarity coefficient (DSC), an overlap-based metric, from the expert annotations. Intraclass correlation coefficient (ICC) scores from ground truth measurements were made for every labelled image. Results Qualitative evaluation by domain experts confirmed consistency and anatomical precision of the outputs across a range of bowel regions and disease activity. Quantitatively, on the validation set our model achieved DSC of 0.73 [0.70 - 0.75], 0.26 [0.23 - 0.28], 0.62 [0.55 - 0.68], 0.63 [0.53 - 0.72], 0.72 [0.64 - 0.79] and 0.41 [0.32 - 0.49] for BW, peritoneal lining, rectus, psoas, IV and IM. Based on BW segmentations, the measurement algorithm achieved an ICC of 0.83 [0.77 - 0.87] between predictions and per frame expert measurements. On the external test dataset, the ICC between an aggregated AI-driven measurement per CL and the mean of all reader measurements was 0.83 [0.73 - 0.9]. Conclusion Unlike prior approaches focused on static frames or derived BWT estimation, this method preserves frame-to-frame continuity, enabling reproducible analysis of CLs with no manual pre-selection of measurement areas. Our model provides identification of many anatomical structures in addition to BWT, essential to moving AI beyond this measure and towards fully automated disease activity monitoring. Conflict of interest: Novak, Kerri L.: Research Grants: Helmsley Trust, Pfizer, Janssen Adboard, consulting fees: Abbvie, Janssen, Pfizer, Pendopharm, Takeda, Elli Lilly, Celltrion, Bristal Myers Non financial support (ultrasound machine) McKesson Pharmcy. Pfizer, Celltrion Mendel, Robert: No conflict of interest Dolinger, Michael: Personal Fees: Michael Dolinger is a consultant for Neruologica., a subsidiary of Samsung Electronics Co., Ltd. Maaser, Christian: Speaker honaria and/or Advisory honaria Abbvie, Alfasigma, Biogen, Falk Foundation, Galapagos, Gilead, J & J, MSD Sharp & Dome, Pfizer, Roche, Samsung, Takeda Gecse, Krisztina B.: Grant: Abbvie, Pfizer Inc, Celltrion and Galapagos/Alfasigma Personal Fees: Consultancy fees from AbbVie, ​Galapagos, Gilead, Immunic Therapeutics, Janssen Pharmaceuticals, Pfizer Inc., and Takeda and speaker’s honoraria from Celltrion, Eli Lilly, Janssen Pharmaceuticals, Pfizer Inc. and Takeda. Nash, Carla: No conflict of interest Smyth, Matthew: No conflict of interest Sagami, Shintaro: Shintaro Sagami has served as an advisory board member, consultant, or speaker for AbbVie, Alimentiv, Bristol Myers Squibb, Celltrion, EA Pharma, Eli Lilly, Ferring Pharmaceuticals, Gilead Sciences, Janssen Pharmaceuticals, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda, and Zeria Pharmaceutical, and has received research funding from Bristol Myers Squibb, EA Pharma, Gilead Sciences, Helmsley Charitable Trust, JIMRO, Kyorin Pharmaceutical, Miyarisan, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Sekisui Medical, Samsung, Takeda, and Zeria Pharmaceutical. Nylund, Kim: Other: PI in clinical trial (Takeda) Ellis, Edward: No conflict of interest Sanghera, Daljinder: No conflict of interest Dr. Flegg, Daniel: No conflict of interest Torisu, Misaki: No conflict of interest Fu, Y. Nancy: No conflict of interest Ernest-Suárez, Kenneth: Consulting/Advisory Board fees: Abbvie, AstraZeneca, Johnson & Johnson, Pfizer, Ferring, Sandoz, SatisfAI, Takeda Johannessen, Solveig: No conflict of interest Gurm, Sunny: No conflict of interest Panaccione, Remo: No conflict of interest Wilkens, Rune Levring: Personal Fees: Janssen, Takeda Denmark, AbbVie, Pfizer Denmark, Alimentiv Byrne, Michael: Founder and shareholder, Dova Health Intelligence

Abstract Background Comparative data on risankizumab (RISA) and upadacitinib (UPA) in Crohn’s disease (CD) are limited. In this preliminary analysis, we assessed treatment persistence with these agents and explored whether the choice should be modified according to disease location. Methods Data from the Czech National Prospective Registry of Biological and Innovative Therapies for Inflammatory Bowel Disease (CREdIT) were analysed to evaluate treatment persistence in adult and paediatric patients with CD who began treatment with RISA or UPA, with a minimum follow-up period of three months. Patients with missing outcomes or dual advanced therapy were excluded. Inverse-probability-of-treatment weighting (IPTW) based on a propensity score including demographic, disease activity and treatment history variables was applied to reduce confounding factors. Treatment persistence was analysed using Kaplan–Meier curves and Cox proportional hazards models, clustered by patient. We evaluated whether disease location (ileal vs non-ileal) altered treatment persistence by using group-specific survival analyses. Results A total of 474 treatment observations were identified in patients receiving RISA or UPA. Following the application of exclusion criteria, the analysis included 370 observations from 323 patients, of which 157 (42%) were on RISA and 213 (58%) were on UPA. Of these, 11 (7%) were paediatric patients in the RISA group and 22 (10%) in the UPA group. The median number of actual lines of advanced therapy was four in both groups, with 38% of RISA observations and 39% of UPA observations representing ≥ 5th treatment line. Groups differed only in age at treatment start (median 38 vs 37 years). Ileal disease only was present in 23 (15%) RISA patients and 28 (13%) UPA patients. Unadjusted data (Figure 1) demonstrated higher persistence of RISA vs. UPA treatment. After balancing the cohort using IPTW, all standardised mean differences between groups were below 0.1. Compared with RISA, UPA was associated with a higher risk of treatment discontinuation (hazard ratio: 2.83; 95% confidence interval: 1.50–6.34). Interaction analysis by disease location was not feasible because no RISA failures occurred in the ileal subgroup. Therefore, only descriptive stratified curves are shown in Figure 2. Conclusion In this preliminary analysis of refractory CD, treatment persistence was greater with RISA than with UPA. These real-world data suggest that RISA may be a more durable treatment option, particularly for patients with ileal CD. However, confirmation in larger patient groups is required. Conflict of interest: Dr. Hradsky, Ondrej: Lectures/congress fees/consultancy from MSD, AbbVie, Takeda, Sandoz, Nutricia, Ferring, Pfizer, and Lilly. Duricova, Dana: Lectures/congress fees/consultancy (outside the scope of the submitted work) from Johnson & Johnson, Takeda, AbbVie, Pfizer, Ferring, Eli Lilly, and Celltrion. Lukás, Milan: Research Support / Clinical trials: Biogen, Takeda, Janssen Consultant / Speaker : Abbvie, Ferring, Takeda, Janssen Speakers Bureau / Advisory Board Member: Pfizer, Roche, Egis, Celltrion, Takeda, Janssen, Eli Lilly Employee: ISCARE a.s./1stMedical Faculty, Charles University, Prague Nedbalova, Lenka: No conflict of interest Bouchner, Luděk: No conflict of interest Pipek, Barbora: Lectures/congress fees/consultancy (outside the scope of the submitted work) from Johnson & Johnson, Takeda, AbbVie, Pfizer, and Eli Lilly. Svoboda, Pavel: Lectures/congress fees/consultancy (outside the scope of the submitted work) from AbbVie, Takeda, Janssen-Cilag, Celltrion, Tillotts, Alfasigma, Sandoz, Pfizer, and Eli Lilly. Siroky, Milan: No conflict of interest Bronsky, Jiri: Lectures/congress fees/consultancy (outside the scope of the submitted work) from AbbVie, Sandoz, Danone-Nutricia, Nestlé, Sanofi, Pfizer, and Vitabalans. Bortlik, Martin: Lectures/congress fees/consultancy (outside the scope of the submitted work) from AbbVie, Takeda, Janssen-Cilag, Celltrion, Roche, AstraZeneca, Biogen, Tillotts, Ferring, Alfasigma, PRO.MED.CS, Sandoz, Bristol-Myers Squibb, Pfizer, and Swedish Orphan Biovitrum.

Abstract Background Transperineal ultrasound (TPUS) has emerged as a non-invasive method for assessing rectal inflammation in ulcerative colitis (UC) and overcomes the limitations of standard intestinal ultrasound in evaluating distal colonic disease. However, TPUS has never been studied in acute severe UC (ASUC). The TRANSPIRE study aimed to determine whether early TPUS parameters can identify steroid non-response in ASUC. Methods In this prospective study, adults admitted with ASUC (per Truelove and Witts criteria) underwent TPUS on admission (T1) and 48±24 hours later (T2). Parameters assessed included rectal bowel wall thickness (BWT) and Doppler activity. Steroid non-response (SNR) was defined as the need for medical rescue therapy. Predictive performance was assessed using comparative statistics and ROC analysis. Results Twelve patients were included, median age 40 years, 66.7% were female. Two patients had proctitis and the remainder had left-sided or pancolitis. Five (41.7%) patients required rescue therapy. Rectal BWT was higher in non-responders at both T1 and T2. Median T1BWT was 7.0mm in responders and 8.4mm in non-responders (p=0.09). T1BWT ≥8.4mm predicted steroid non-response (sensitivity 60%, specificity 100%, AUROC 0.80) and outperformed admission UCEIS (AUROC 0.59). Median T2BWT was 5.6mm in responders and 6.6mm in non-responders (p=0.02). T2BWT ≥6.6mm similarly predicted steroid non-response (sensitivity 60%, specificity 100%, AUROC 0.80). A 20% reduction in BWT from T1 to T2 identified SNR (sensitivity 80%, specificity 85.7%, PPV 80%, NPV 85.7%, OR 24 (1.0-45), AUROC 0.83). Doppler activity did not significantly differ between groups or enhance prediction beyond BWT. Conclusion TRANSPIRE is the first study to evaluate TPUS in ASUC. T1 and T2 rectal BWT can be used to identify corticosteroid non-response, supporting TPUS as a promising rectal-focused, non-invasive bedside tool in ASUC. Larger studies are needed to validate these findings. Conflict of interest: Subhaharan, Deloshaan: No conflict of interest Sagami, Shintaro: Shintaro Sagami has served as an advisory board member, consultant, or speaker for AbbVie, Alimentiv, Bristol Myers Squibb, Celltrion, EA Pharma, Eli Lilly, Ferring Pharmaceuticals, Gilead Sciences, Janssen Pharmaceuticals, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda, and Zeria Pharmaceutical, and has received research funding from Bristol Myers Squibb, EA Pharma, Gilead Sciences, Helmsley Charitable Trust, JIMRO, Kyorin Pharmaceutical, Miyarisan, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Sekisui Medical, Samsung, Takeda, and Zeria Pharmaceutical. Haig, Adam: No conflict of interest Mohsen, Waled: No conflict of interest Kakkadasam Ramaswamy, Pradeep: None

Abstract Background Despite the expanding therapeutic armamentarium for inflammatory bowel disease (IBD), a significant proportion of patients experience suboptimal response, loss of response (LOR), or treatment-limiting side effects. Therapy optimisation is increasingly recognised as a key strategy to enhance treatment efficacy, durability, and safety. The ECCO topical review on therapy optimisation aimed to provide evidence-based and expert-driven guidance on optimising currently available IBD therapies, including anti-TNFs, anti-integrins, anti-IL-23 agents, and small molecules. Methods An expert multidisciplinary panel divided into four working groups (WGs) conducted a comprehensive review of the literature on pharmacokinetics, therapeutic drug monitoring (TDM), dose intensification, immunogenicity, and predictors of response to optimised treatment. Evidence was appraised through systematic searches and structured discussions. Consensus statements were generated using PICO methodology, and recommendations were developed through iterative group consensus. Results Thirty-five statements were formulated across therapeutic classes. For anti-TNF agents, higher trough levels during induction and maintenance were associated with improved outcomes; proactive TDM and short-term combination with immunomodulators were recommended strategies to mitigate immunogenicity. For vedolizumab, interval shortening may recapture response, while combination with immunomodulators provided no consistent benefit. For ustekinumab and risankizumab, extended induction and interval shortening were viable options in selected patients with partial response or LOR. For small molecules, upadacitinib and tofacitinib dose intensification showed promise in ulcerative colitis (UC), though data for Crohn’s disease (CD) remain limited. Safety signals across dose-optimised strategies were generally comparable to standard dosing. Conclusion Therapy optimisation in IBD, through proactive monitoring and personalised dose adjustment, holds promise for improving patient outcomes and drug durability. This ECCO topical review offers structured, agent-specific guidance to support therapeutic decision-making across a spectrum of biologics and small molecules in both UC and CD. Conflict of interest: Queiroz, Natalia: Personal Fees: NSFQ has served as a speaker and advisory board member of Janssen, Takeda and Abbvie. 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. D’Amico, Ferdinando: Grant: ECCO fellowship grant 2020 ECCO grant 2021 Personal Fees: F D’Amico has served as a speaker for Abbvie, Alfasigma, Ferring, Lilly, Sandoz, Janssen, Fresenius Kabi, Galapagos, Giuliani, MSD, Pfizer, Takeda, Tillotts, and Omega Pharma he also served as an advisory board member for Abbvie, AnaptysBio, Ferring, Fresenius Kabi, Galapagos, Janssen, Lilly, MSD, Takeda, and Nestlè. Katsanos, Konstantinos: AbbVie, Amgen, Athos, Αenorasis, Biocon,Biogaia, Drugssales Ltd, Epsilon Health, Falk, Faran, Ferring, Genesis, Grifols S.A., Hospital line, Johnson & Johnson, COPER, MSD, Biocon, Pfizer, Potamitis Medicare, Rafarm, Petsiavas, Shire,Takeda, Vianex, Lilly Lobatón Ortega, Triana: Grant: Abbvie, Ferring, Viatris, MSD, EG, Mundipharma, Biogen, Janssen, Pfizer, Takeda, Galapagos, Afasigma and Sandoz. Personal Fees: Speaker fees from MSD, Abbvie, Janssen, Amgen, Fresenius Kabi, Galapagos, Viatris, Ferring, Celltrion, Alfasigma, Lilly and Takeda. Consultancy fee from Janssen, Galapagos, Alfasigma, Amgen, Bristol Myers, Squibb Fresenius Kabi, Takeda and Abbvie Plevris, Nikolas: Speaker fees / travel support from Abbvie, Pfizer, Janssen, Lilly, Ferring Rodríguez-Lago, Iago: Financial support for traveling and educational activities from or has served as an advisory board member for Abbvie, Adacyte, Alfasigma, Biogen, Chiesi, Faes Farma, Ferring, Fresenius Kabi, Galapagos, Johnson & Johnson, Eli Lilly, Mirum Pharmaceuticals, Merck, Pfizer, Roche, Takeda, and Tillotts Pharma. Research support from AbbVie Ungar, Bella: Bella Ungar has recieved lecture fees / consultation fees from Ely Lilly, Abbvie, Takeda, Padagis Yanai, Henit: Grant: Pfizer, ISF Personal Fees: AbbVie, Janssen, Pfizer, Takeda, Bristol Myers Squibb, and Elly Lilli. Parra Izquierdo, Leidy Viviana: No conflict of interest Hanzel, Jurij: Speaker’s fees from Abbvie, Eli Lilly, Janssen, and Takeda, and consulting fees from Alimentiv Inc and Janssen Ernest-Suárez, Kenneth: Consulting/Advisory Board fees: Abbvie, AstraZeneca, Johnson & Johnson, Pfizer, Ferring, Sandoz, SatisfAI, Takeda Krznarić, Željko: Speakers honoraria (Abbott, Abbvie, Biocon, Celltrion/ Octal Pharma, Fresenius, Eli Lilly, Pharmas, Pfizer, Sobi, Takeda, Nestle, Nutricia, Baxter, Janssen, MSD). Advisory boards Tavares de Sousa, Helena: Takeda, AbbVie, Janssen, Pfizer, Ferring, Biogen, Lilly - for presenting or advisory board Non-financial Support: Abbvie, Takeda, Janssen, Ferring, Faez Pharma, Tillots, Falk Pharma Kopylov, Uri: Grant: Takeda, Janssen,Abbvie, Medtronic, Ely Lilly Other: Takeda, Janssen, Ely Lilly, Roche, Celtrion, Abbvie, Medtronic, CTS, Pfizer, BMS- speaker and advisory fees

Abstract Background Etrasimod is a novel oral selective sphingosine 1-phosphate receptor (S1PR) modulator recommended for induction and maintenance of remission in moderate-to-severe ulcerative colitis (UC). Safety considerations include potential cardiac conduction abnormalities warranting baseline electrocardiography (ECG). In addition, ophthalmologic assessment with optical coherence tomography (OCT) is recommended within 3 months of starting treatment. Real-world evidence of its safety and effectiveness remains limited. Methods A retrospective observational study was conducted across six tertiary centers. All patients with UC treated with etrasimod at each centre were included. Demographic data, cardiovascular and ophthalmologic assessments, adverse events, treatment persistence, disease activity indices (SCCAI, UCEIS) and faecal calprotectin at baseline, 3 and 6 months were collected. Results 193 patients were included, with a median age of 38 years (IQR 29–49.5). 19.7% of patients had proctitis, 44.6% left-sided disease, 31.6% extensive UC, 1.0% IBD-U, and 3.1% unknown. 123 (63.7%) were advanced therapy (AT)-naïve. Of those exposed to AT, the median (range) number of ATs was 2 (0-9). Baseline ECG was performed in 97.4% with six (3.1%) patients requiring first dose ambulatory cardiac monitoring. OCT was completed in 115/165 (69.7%) patients within three months of starting therapy. Adverse events were reported in 30 (15.5%) patients: headache (23.3%), lymphopaenia (16.6%, lymphocyte count <0.5 × 109/L), blurred vision (13.3%), and dizziness or lightheadedness (13.3%). One case of bradycardia (HR < 45bpm) and one case of first-degree atrioventricular block were reported. No major ophthalmologic complications were observed. Treatment persistence at the time of analysis was 63.2% with a median follow-up of 7 months (IQR 3-10.8). The main reasons for treatment discontinuation were lack of clinical response (47 patients, 24.4%) and adverse events (12 patients, 6.2%).165 (86%) patients completed 12 weeks of treatment at which time significant improvements were observed in disease activity and biomarkers; SCCAI scores (n = 83) decreased from 4.6 to 3.1 (p < 0.0001), faecal calprotectin (n = 50) fell from 942 µg/g to 478 µg/g (p = 0.002), and UCEIS (n = 50) from 4.1 to 2.8 (p < 0.0001). 119 (61.6%) patients had ≥6 months of follow-up. Conclusion This real-world study of etrasimod demonstrated a safety and efficacy profile consistent with data from the registration studies of etrasimod in UC, supporting its role in clinical practice. Ongoing, well curated real world datasets will enhance our understanding of this novel mechanism of action further. Reference: Sandborn WJ, Vermeire S, PeyrinBiroulet L, et al. Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, doubleblind, placebocontrolled, phase 3 studies. Lancet. 2023;401(10383):11591171. doi:10.1016/S01406736(23)000612 Conflict of interest: Mx. Vayreda, Eva: No conflict of interest Vasconcellos S. Reis, Paola: No conflict of interest Matini, Lawrence: Speaker fees: AbbVie, Galapagos, Bristol Myers Squibb Punj Sharda, Anita: I declare that I have no conflicts of interest. Dunbar, Grace: No conflicts Hall, Richard: Speaker fees - Takeda Lopezosa Estepa, Teresa: No conflict of interest Williams, Stephanie: No conflict of interest Islam, Samiha: No conflict of interest Javed, Anum: No conflict of interest Patel, Kamal Vijaykant: Received honoraria for educational meetings and speaker fees from Abbvie, Janssen, Takeda, Dr. Falk Pharma, PredictImmune, Pfizer, and Ferring and has received advisory board fees from Abbvie, Galapagos, Pfizer, and Janssen. He has also received a grant from AbbVie to support research. Honap, Sailish: Sailish Honap has served as a speaker, consultant, advisory board member, and/or received travel grants from AbbVie, AlfaSigma, Banook Group, Ferring, Johnson & Johnson, Lilly, Pharmacosmos, Pfizer, and Takeda. Mehta, Shameer: Personal fees: Pfizer, Takeda, Johnson & Johnson Walsh, Alissa: Grant: Alfasigma, Helmsley Trust, Johnson & Johnson, Pfizer, Takeda Personal Fees: AbbVie, Alfasigma, Bristol Meyers Squibb, Dr Falk, Ferring, Johnson & Johnson, Lilly, Pfizer, Takeda, Tillotts Alexander, James: James has received speaker fees from Pfizer, Abbvie, Takeda and Janssen. He has received travel grants and support to attend meetings from Lilly, Tillotts Pharma, Takeda and Celltrion. Irving, Peter Miles: Grant: MSD, Pfizer, Takeda, Celltrion, Galapagos Personal Fees: AbbVie, Arena, BMS, Boomerang Medical, Celgene, Celltrion, Falk Pharma, Ferring, Galapagos, Genentech, Gilead, Hospira, Janssen, Lilly, MSD, Pfizer, Pharmacosmos, Prometheus, Roche, Sandoz, Samsung Bioepis, Sapphire Medical, Sandoz, Shire, Takeda, Tillotts, Topivert, VH2, Vifor Pharma, Warner Chilcott

Abstract Background Mirikizumab (MRK) is a monoclonal antibody targeting the IL-23 p19 subunit that has demonstrated efficacy in pivotal trials for moderate-to-severe ulcerative colitis (UC). Real-world data in patients with multi-refractory disease are still limited. We aimed to assess the short- and mid-term effectiveness, safety, and treatment persistence of MRK in routine clinical practice. Methods We conducted a retrospective observational study of consecutive adult UC patients who initiated MRK between June 2024 and June 2025 and completed induction. The primary endpoint was symptomatic remission at week 12. Secondary endpoints included clinical remission at week 24, biochemical remission (faecal calprotectin <250 µg/g) at weeks 12 and 24, adverse events, and treatment persistence. Symptomatic remission and clinical response were defined according to PRO2 (stool frequency and rectal bleeding subscores). Results Thirty-three patients were included (24% women), with a median age of 58 years and a median disease duration of 15.6 years. Most patients had prior exposure to advanced therapies: 85% had received anti-TNF agents, 64% vedolizumab and 58% ustekinumab; 60.6% had been treated with three and 24.2% with four previous advanced lines. Disease extent was E2 in 48% and E3 in 52%, including three patients with an ileoanal pouch. Baseline disease activity was moderate, with a median partial Mayo score of 4±2. MRK was prescribed as monotherapy in 77%; 33% received co-induction (24% corticosteroids, 11% apheresis), and 39.4% underwent extended induction. At week 12, 56.5% achieved symptomatic remission and 86.9% a clinical response. At week 24 (n = 10), 70% were in clinical remission and 90% had a clinical response. Median faecal calprotectin fell from 2964 µg/g at baseline to 983 µg/g at week 12 and 586 µg/g at week 24 (p < 0.001), with biochemical remission rates of 28.6% and 31.2%, respectively. Two patients developed pruritus: one mild, self-limiting case with successful re-challenge after negative allergy testing, and one confirmed delayed allergy. Overall, 81.8% of patients remained on treatment at last follow-up, while six patients (18.2%) discontinued MRK (four due to treatment failure, one by patient choice and one because of an adverse event). Median follow-up under MRK was 24 weeks (mean 29.9; range 4–71). Conclusion In this real-world cohort of long-standing, highly pre-treated UC, mirikizumab achieved high rates of PRO2-defined clinical response and remission, with a favourable short-term safety profile and high treatment persistence. Conflict of interest: Dr. Elosua Gonzalez, Alfonso: I have served as a speaker, consultant, or advisory board member, and has received educational support from AbbVie, Johnson & Johnson, Adacyte, Takeda, Faes Farma, Ferring, and Tillotts Pharma.** Zabalza, Lucía: LZ has received financial support to attend courses and congresses from AbbVie, Adacyte, Johnson & Johnson, Takeda, Ferring, Faes Farma, and Cassen. Vicuña, Miren: No conflict of interest Rubio, Saioa: No conflict of interest Nantes Castillejo, Oscar: ON has served as speaker, consultant or research or education funding from MSD, Abbvie, Pfizer, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Faes-Farma, Adacyte therapeutics and Sanofi-Aventis. Rodriguez, Cristina: CR has received scientific advice, support for research and/or educational activities, research grants, and has participated in consultancy services from Abbvie, Adacyte, MSD, Janssen, Pfizer, Tillots, Ferring, Falk, Takeda, Lilly, and Galapagos

Abstract Background Endoscopy is commonly used to assess disease activity in Crohn’s disease (CD), but it is invasive and limited to mucosal evaluation. We investigated whether intestinal ultrasound (IUS) and leucine-rich α-2 glycoprotein (LRG) can predict relapse in CD and support treat-to-target monitoring. Methods This single-centre retrospective observational study enrolled CD patients from 2019 to 2024 who underwent paired IUS and LRG testing. Relapse within the 1-year observation period was defined as treatment escalation, hospitalisation, or surgery. The predictive performance of C-reactive protein (CRP), IUS [assessed using the international bowel ultrasound segmental activity score (IBUS-SAS)], and LRG was evaluated using log-rank tests and Cox proportional hazards models. Hazard ratios (HRs) per one-unit increase in IBUS-SAS and LRG were also calculated using Cox models. Cut-off values for CRP, IBUS-SAS, and LRG were derived from receiver operating characteristic (ROC) analysis using the Youden Index and used for stratified analyses. Results A total of 117 IUS assessments were performed in 78 patients; 38 (32%) relapsed. Kaplan–Meier analysis demonstrated significant differences in relapse-free survival according to CRP, IBUS-SAS, and LRG. In Cox models, all three markers were significant predictors in univariable analysis (all P < 0.05), but only CRP remained significant in the multivariable model (P = 0.02; Table 1). The optimal cut-off values were 24 for IBUS-SAS and 13 for LRG. In univariable Cox proportional hazards analyses restricted to patients with baseline CRP < 0.13 mg/dL, both LRG (HR 9.76; 95% CI = 1.17–81.2) and IBUS-SAS (HR 5.53; 95% CI = 1.07–28.5) were significant predictors, as reflected by Kaplan–Meier curves (Figure 1). Conclusion LRG, IBUS-SAS, and CRP each predict relapse in CD. Both LRG and IBUS-SAS can stratify relapse risk even when CRP is negative, supporting their combined use to monitor transmural inflammation and guide timely treatment optimisation. Conflict of interest: Ms. Inoue, Nanako: No conflict of interest Sagami, Shintaro: Shintaro Sagami has served as an advisory board member, consultant, or speaker for AbbVie, Alimentiv, Bristol Myers Squibb, Celltrion, EA Pharma, Eli Lilly, Ferring Pharmaceuticals, Gilead Sciences, Janssen Pharmaceuticals, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda, and Zeria Pharmaceutical, and has received research funding from Bristol Myers Squibb, EA Pharma, Gilead Sciences, Helmsley Charitable Trust, JIMRO, Kyorin Pharmaceutical, Miyarisan, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Sekisui Medical, Samsung, Takeda, and Zeria Pharmaceutical. Komatsu, Moeko: No conflict of interest Asonuma, Kunio: Kunio Asonuma has served as a speaker for AbbVie, Takeda Pharmaceutical, Mochida Pharmaceutical, EA Pharma, Pfizer, Mitsubishi-Tanabe Pharma, and KISSEI PHARMACEUTICAL CO., LTD. Nogami, Akira: Akira Nogami has received speaking fees from Abbvie GK and Mochida Pharmaceutical. Shibui, Shunsuke: Shunsuke Shibui has received speaking fees from Abbvie GK and Mochida Pharmaceutical. Suzuki, Keita: No conflict of interest Nakamura, Kenta: No conflict of interest Umeda, Satoko: No conflict of interest Matsubayashi, Mao: No conflict of interest Nakano, Masaru: Masaru Nakano has received speaker or consultancy fees from Covidien, Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Zeria Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., and Nippon Kayaku Co., Ltd. and research funding from Mitsubishi Tanabe Pharma Corporation and the Japanese Foundation for Research and Promotion of Endoscopy. 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

Abstract Background Discontinuation of anti-TNF agents after sustained remission leads to relapse in about half of cases within one year, but data on other biologics remain limited. This study aimed to assess the risk of recurrence after vedolizumab (VDZ) discontinuation in patients with inflammatory bowel disease (IBD) who achieved sustained steroid-free remission on standard maintenance regimen. Methods Patients with IBD who stopped VDZ after at least 6 months of steroid-free remission (defined as combined clinical and endoscopic remission at last assessment) between 2017 and 2025 were retrospectively included. A control group of patients maintaining VDZ after a comparable remission period was used. The primary outcome was the rate of any recurrence (clinical, biochemical, or endoscopic) in the discontinuation vs the control group. Secondary outcomes included the evaluation of clinical, biochemical, and endoscopic recurrence rates. Univariable and multivariable Cox regression models were used to identify predictors of relapse, with results expressed as hazard ratios (HRs) and 95% confidence intervals (CIs). Recurrence-free survival was analysed with Kaplan-Meier curves and compared with the log-rank test. Results Overall, 165 patients were included: 67 in the discontinuation group and 98 controls, with a median follow-up of 36 months (IQR 16-51) (Table 1). At 12 months, 15 (22%) patients in the discontinuation group vs 4 (4%) in the control group showed any recurrence (p < 0.01). Over the entire follow-up, 41 patients (61%) who discontinued and 18 patients (18%) who continued VDZ experienced any recurrence (p < 0.01). Kaplan-Meier analysis showed a significantly higher recurrence-free survival among patients continuing VDZ across all definitions of recurrence (Figure 1). VDZ discontinuation was independently associated with a higher risk of any recurrence at both univariable (HR 5.2, 95%CI 2.9-9.1, p < 0.01) and multivariable analysis (HR 5.2, 95%CI 2.9-9.6, p < 0.01), with no significant effect of other covariates. Increased risks in the discontinuation group were also observed for secondary endpoints, including endoscopic recurrence (HR 3.6, 95%CI 1.7-7.9, p < 0.01). Among patients who relapsed after discontinuation, 26 (63%) restarted VDZ, of whom 6 (23%) achieved clinical remission at 6 months. Conclusion VDZ discontinuation, even after sustained remission, carries a high recurrence risk and low recapture rates, suggesting to approach withdrawal cautiously pending further evidence. Conflict of interest: Dragoni, Gabriele: Grant: ECCO Grant 2020 ECCO/AOCC Travel Grant 2021 ECCO IIS Registry Grant 2023 ECCO/IBUS Research Grant 2023 Personal Fees: - Speaker’s fees from: 2020: Novartis 2022: Janssen 2023: Alfasigma, Janssen, Pfizer, and Takeda 2024: Ferring, Johnson & Johnson, Eli Lilly, Pfizer, and Takeda 2025: Abbvie, Alfasigma, Ferring, Eli Lilly, LionHealth, Pfizer, Takeda - Advisory board fees from: 2023: Celltrion Healthcare and Pfizer 2024: AbbVie 2025: AbbVie, Johnson & Johnson Dr. Innocenti, Tommaso: Speaker fees from Aurora Biofarma, and Ferring. Travel grants from Abbvie, Alfasigma, Celltrion, Eli Lilly, Ferring, Malesci, Pfizer. Festa, Stefano: Personal Fees: Consultant and/or Advisory board member for: Takeda, Johnson & Johnson, Pfizer, Galapagos, Abbvie, Ferring, Eli Lilly Felice, Carla: Advisory board for AbbVie, MSD, J & J . Rizzello, Fernando: No conflict of interest Viola, Anna: No conflict of interest Baccini, Flavia: No conflict of interest Balestrieri, Paola: Advisory board for Alfasigma- Janssen- Abbvie- Takeda- Eli Lilly Pugliese, Daniela: Consultant/Lectures fees from: AbbVie, Takeda, Johnson, Pfizer, Alfasigma, MSD, Lilly, Celltrion. Mattana, Marco: No conflict of interest Cocomazzi, Francesco: No conflict of interest Savarino, Edoardo Vincenzo: Personal Fees: Takeda, Abbvie, MSD, Janssen, Sofar Zappia, Federica: No conflict of interest Panarese, Alba: No conflict of interest Ribaldone, Davide Giuseppe: Davide Giuseppe Ribaldone declares the following paid consultancies, lecture fees for the past two years: Johnson & Johnson, Takeda, Celltrion, Alfasigma, Pfizer, Eli Lilly, Abbvie, Sandoz Bertani, Lorenzo: No conflict of interest Piagnani, Alessandra: No conflict of interest Bezzio, Cristina: Personal Fees: I received consulting/advisory board/lecture fees from Alfa Sigma, AbbVie, Celltrion, Eli Lilly, Ferring, Gilead, Johnson & Johnson MSD, Pfizer and Takeda Di Paolo, Dhanai: No conflict of interest Viganò, Chiara: Consultancy and lecture fees from: AbbVie, Galapagos, Janssen-Cilag, Johnson & Johnson, Pfizer, Takeda, Celltrion, Alfasigma, Eli Lilly and research grant from Celltrion and Pfizer. Spagnuolo, Rocco: No conflict of interest Ricci, Chiara: No conflict of interest Mocci, Giammarco: No conflict of interest Fantini, Massimo Claudio: MCF has acted as a consultant for: AbbVie, AlfaSigma, Celgene, Celltrion, Gilead, Pfizer, MSD, Bristol-Meyer, Takeda, Johnson & Johnson, Roche, Galapagos, Biogen, Sandoz, Eli-Lilly, Lionhealth, Teva, Giuliani, Dr Falk Pharma, Sanofi he has received financial support for research from Johnson & Johnson and Pfizer.